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Keywords = immunotherapy in lymphoma 2

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17 pages, 5258 KiB  
Article
EGFR-Mutant Lung Adenocarcinoma Cell-Derived Exosomal miR-651-5p Induces CD8+ T Cell Apoptosis via Downregulating BCL2 Expression
by Chao Zhao, Lei Cheng, Aiwu Li, Haowei Wang, Xuefei Li and Jun Xu
Biomedicines 2025, 13(2), 482; https://doi.org/10.3390/biomedicines13020482 - 15 Feb 2025
Viewed by 1063
Abstract
Background: The efficacy of programmed cell death 1 (PD-1) or ligand 1 (PD-L1) inhibitors in epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) patients is not satisfactory. Studies have indicated that the ratio of CD8+ tumor infiltration lymphocytes [...] Read more.
Background: The efficacy of programmed cell death 1 (PD-1) or ligand 1 (PD-L1) inhibitors in epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) patients is not satisfactory. Studies have indicated that the ratio of CD8+ tumor infiltration lymphocytes (TILs) was associated with immunotherapy efficacy; however, it was significantly lower in EGFR-mutant than wild type patients. The underlying mechanisms need to be studied. Methods: Database analysis, clinical specimens, small RNA sequencing, and single-cell sequencing were used to analyze miRNA expression and immune cell infiltration. Cell co-culture and flow cytometry were conducted to detect immune cell apoptosis. The mouse model was performed to analyze the influence of miR-651-5p antagomirs on the tumor microenvironment. Results: The miR-651-5p was found to be highly expressed in EGFR-mutant lung adenocarcinoma cell-derived exosomes, which could promote CD8+ T cell apoptosis, while the miR-651-5p inhibitor decreased the ratio of PC9-secreted exosomes and induced apoptosis. Mechanistically, the EGFR signaling pathway promoted the expression of miR-651-5p by activating the transcription factor Fos proto-oncogene (FOS) in EGFR-mutant lung adenocarcinoma cell lines. B-cell lymphoma 2 (BCL2) was the target of miR-651-5p, and miR-651-5p could promote T cell apoptosis by inhibiting BCL2 expression. In addition, the miR-651-5p antagomir increased T cell infiltration and enhanced the efficacy of the PD-1 inhibitor treating the EGFR-mutant lung adenocarcinoma humanized mouse model. Conclusions: EGFR-mutant lung adenocarcinoma promotes T cell apoptosis through exosomal miR-651-5p. miR-651-5p antagonists increase immune cell infiltration and enhance the anti-tumor effect of PD-1 inhibitor, suggesting a new combination therapy to improve the efficacy of immunotherapy in EGFR-mutant NSCLC patients. Full article
(This article belongs to the Section Cell Biology and Pathology)
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9 pages, 2367 KiB  
Article
Insights Through the Endoscope: A Retrospective Study Unraveling the Macroscopic Features of Primary Colorectal Lymphoma
by Jacob J. Gries, Bing Chen, Steven M. Ney, Idorenyin Udoeyo and Duane E. Deivert
Gastrointest. Disord. 2025, 7(1), 14; https://doi.org/10.3390/gidisord7010014 - 13 Feb 2025
Viewed by 786
Abstract
Introduction: Primary colorectal lymphoma (PCL) is a very rare disease with limited information regarding its macroscopic features. This retrospective descriptive study aims to identify the macroscopic characteristics of PCL and explore treatment trends and outcomes with respect to histopathologic subtypes. Methods: [...] Read more.
Introduction: Primary colorectal lymphoma (PCL) is a very rare disease with limited information regarding its macroscopic features. This retrospective descriptive study aims to identify the macroscopic characteristics of PCL and explore treatment trends and outcomes with respect to histopathologic subtypes. Methods: This IRB-approved study from a large academic medical center identified 66 patients with colorectal lymphoma from 1998 to 2022 from a tumor registry. Thirty-four patients met the inclusion criteria of having PCL with available endoscopic data. The macroscopic features of each lesion were identified. Treatment trends and outcomes were examined at the patient level. Data were described using frequency and percentages for categorical characteristics and the median and interquatile range (IQR) for continuous outcomes. Results: A total of 77 PCL lesions were identified. Most were identified on screening or surveillance colonoscopies or colonoscopies performed after abnormal imaging (61.8%). Diffuse large B cell lymphoma (DLBCL) had the highest prevalence (N = 24), followed by follicular lymphoma (n = 21), mantle cell (n = 16), mucosa-associated lymphoid tissue (MALT) (n = 14), then Burkitt’s (n = 2). More mantle cell (93.8%) and follicular (90.5%) lymphomas were sessile. More MALT lymphomas were ulcerated (71.4%). A higher proportion of follicular (76.2%) and mantle cell (71.4%) lymphomas were diminutive (≤5 mm). More MALT (78.6%), DLBCL (75.0%), and Burkitt’s (100%) were large (≥20 mm). More lesions were found in the sigmoid colon (26.0%), followed by the rectum (22.1%), transverse colon (18.2%), cecum (18.2%), descending colon (10.4%), and ascending colon (5.2%). Overall, most underwent immunotherapy (61.3%) and did not have radiation therapy (81.3%), endoscopic resection (75.0%), and surgery (68.8%). Patients with DLBCL demonstrated higher rates of chemotherapy (70.6%), immunotherapy (87.5%), and remission after intervention (52.9%). Conclusions: Primary colorectal lymphomas display distinct macroscopic features and appear in different locations depending on the histopathologic subtype. Most cases are identified at early stages on screening colonoscopies and demonstrate a 75% two-year survival rate. Full article
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28 pages, 1127 KiB  
Review
Unveiling the Role of HGF/c-Met Signaling in Non-Small Cell Lung Cancer Tumor Microenvironment
by Shuxi Yao, Xinyue Liu, Yanqi Feng, Yiming Li, Xiangtian Xiao, Yuelin Han and Shu Xia
Int. J. Mol. Sci. 2024, 25(16), 9101; https://doi.org/10.3390/ijms25169101 - 22 Aug 2024
Cited by 8 | Viewed by 3858
Abstract
Non-small cell lung cancer (NSCLC) is characterized by several molecular alterations that contribute to its development and progression. These alterations include the epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), human epidermal growth factor receptor 2 (HER2), and mesenchymal–epithelial transition factor (c-MET). [...] Read more.
Non-small cell lung cancer (NSCLC) is characterized by several molecular alterations that contribute to its development and progression. These alterations include the epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), human epidermal growth factor receptor 2 (HER2), and mesenchymal–epithelial transition factor (c-MET). Among these, the hepatocyte growth factor (HGF)/c-MET signaling pathway plays a crucial role in NSCLC. In spite of this, the involvement of the HGF/c-MET signaling axis in remodeling the tumor microenvironment (TME) remains relatively unexplored. This review explores the biological functions of the HGF/c-MET signaling pathway in both normal and cancerous cells, examining its multifaceted roles in the NSCLC tumor microenvironment, including tumor cell proliferation, migration and invasion, angiogenesis, and immune evasion. Furthermore, we summarize the current progress and clinical applications of MET-targeted therapies in NSCLC and discuss future research directions, such as the development of novel MET inhibitors and the potential of combination immunotherapy. Full article
(This article belongs to the Section Molecular Oncology)
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11 pages, 1035 KiB  
Systematic Review
The Role of [18F]FDG PET/CT in Predicting Toxicity in Patients with NHL Treated with CAR-T: A Systematic Review
by Natale Quartuccio, Salvatore Ialuna, Sabina Pulizzi, Dante D’Oppido, Stefania Nicolosi and Antonino Maria Moreci
Tomography 2024, 10(6), 869-879; https://doi.org/10.3390/tomography10060066 - 3 Jun 2024
Cited by 3 | Viewed by 2150
Abstract
CAR-T-cell therapy, also referred to as chimeric antigen receptor T-cell therapy, is a novel method in the field of immunotherapy for the treatment of non-Hodgkin’s lymphoma (NHL). In patients receiving CAR-T-cell therapy, fluorodeoxyglucose Positron Emission Tomography/Computer Tomography ([18F]FDG PET/CT) plays a [...] Read more.
CAR-T-cell therapy, also referred to as chimeric antigen receptor T-cell therapy, is a novel method in the field of immunotherapy for the treatment of non-Hodgkin’s lymphoma (NHL). In patients receiving CAR-T-cell therapy, fluorodeoxyglucose Positron Emission Tomography/Computer Tomography ([18F]FDG PET/CT) plays a critical role in tracking treatment response and evaluating the immunotherapy’s overall efficacy. The aim of this study is to provide a systematic review of the literature on the studies aiming to assess and predict toxicity by means of [18F]FDG PET/CT in patients with NHL receiving CAR-T-cell therapy. PubMed/MEDLINE and Cochrane Central Register of Controlled Trials (CENTRAL) databases were interrogated by two investigators to seek studies involving the use of [18F]FDG PET/CT in patients with lymphoma undergoing CAR-T-cell therapy. The comprehensive computer literature search allowed 11 studies to be included. The risk of bias for the studies included in the systematic review was scored as low by using version 2 of the “Quality Assessment of Diagnostic Accuracy Studies” tool (QUADAS-2). The current literature emphasizes the role of [18F]FDG PET/CT in assessing and predicting toxicity in patients with NHL receiving CAR-T-cell therapy, highlighting the evolving nature of research in CAR-T-cell therapy. Additional studies are warranted to increase the collected evidence in the literature. Full article
(This article belongs to the Section Cancer Imaging)
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15 pages, 565 KiB  
Article
Immune Checkpoint Inhibition in Pediatric Oncology Patients: A Single-Institution Experience
by Natalia Wojciechowska, Kaci Orr, Karen Albritton, Kenneth Heym, Kelly Vallance, Lauren Murray, Rocio Aguilar and Anish Ray
Hemato 2024, 5(1), 66-80; https://doi.org/10.3390/hemato5010007 - 6 Mar 2024
Viewed by 2228
Abstract
Immunotherapy has emerged as a promising treatment approach in oncology, as it is specifically designed to boost the strength and accuracy of the immune system, allowing it to target tumor cells but spare non-tumor tissue. This treatment not only demonstrates potential for improved [...] Read more.
Immunotherapy has emerged as a promising treatment approach in oncology, as it is specifically designed to boost the strength and accuracy of the immune system, allowing it to target tumor cells but spare non-tumor tissue. This treatment not only demonstrates potential for improved clinical outcomes but may also be associated with fewer adverse effects compared to traditional therapies. Despite its early success, the application of immunotherapy has largely been limited to adult cancer patients, with slow adoption noted in the treatment of pediatric cancer patients. Our objective is to demonstrate a single institution’s experience with immunotherapy in pediatric cancer patients and to discuss the use of these treatment modalities in this unique patient population. We performed a retrospective chart review and identified patients who received immune checkpoint inhibitors (ICIs) and/or underwent immunohistochemistry (IHC) testing for programmed death ligand 1 (PD-L1), quantification of tumor mutational burden (TMB), and classification of microsatellite instability (MSI) status. In total, we identified seven pediatric cancer patients who received therapy with ICIs. Four of these patients demonstrated positive PD-L1 expression, high TMB, and/or MSI-high status. These patients were treated with nivolumab alone or in combination with ipilimumab or brentuximab. The diagnoses included: multifocal epithelioid and spindle cell hemangioma (n = 1); metastatic melanoma (n = 2); histiocytic sarcoma (n = 1); rectal adenocarcinoma in the setting of constitutional mismatch repair deficiency syndrome (CMMRD) (n = 1); and Hodgkin lymphoma (n = 2). The patients received between four and nineteen cycles of immunotherapy. Immunotherapy-related adverse events included: mild allergic reaction; prodromal symptoms; anemia; neutropenia; transaminitis; endocrinopathies; and self-limiting neuritis. Of the seven patients, three are still being treated with immunotherapy (the patients with rectal adenocarcinoma, metastatic melanoma, and multifocal epithelioid and spindle cell hemangioma) with positive treatment responses observed on imaging, one is being treated with other modalities (the patient with Hodgkin lymphoma), two have achieved remission (the patients with metastatic melanoma and Hodgkin lymphoma), and one has relapsed (the patient with histiocytic sarcoma). The three patients who completed their immunotherapy regimens have been followed for 1 month, 4 months, and 10 months, respectively. This report of a single-institution experience with immunotherapy in pediatric cancer patients highlights the positive impact immunotherapy can have, especially when utilized to treat relapsed/refractory malignancies, as tumor regression or stabilization of disease burden was achieved in six of the patients described (CR = 2; PR = 4). Further research is needed to accurately identify pediatric oncology patients who could benefit from immunotherapy. Full article
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23 pages, 2047 KiB  
Systematic Review
Therapeutic Vaccines for Follicular Lymphoma: A Systematic Review
by Andrei Suponin, Pavel Zhelnov, Artem Potanin, Andrey Chekalov, Aleksandr Lomazov, Kseniia Vladimirova, Kirill Lepik and Albert Muslimov
Pharmaceuticals 2024, 17(3), 272; https://doi.org/10.3390/ph17030272 - 21 Feb 2024
Viewed by 2870
Abstract
(1) Background: We aimed to estimate the pooled effectiveness and safety of vaccination in follicular lymphoma (FL) and discuss implications for immunotherapy development. (2) Methods: We included randomized trials (RCTs) of therapeutic vaccines in patients with FL. Progression-free survival (PFS) was the primary [...] Read more.
(1) Background: We aimed to estimate the pooled effectiveness and safety of vaccination in follicular lymphoma (FL) and discuss implications for immunotherapy development. (2) Methods: We included randomized trials (RCTs) of therapeutic vaccines in patients with FL. Progression-free survival (PFS) was the primary outcome. We searched databases (PubMed, Embase, Scopus, Web of Science Core, medRxiv) and registries (PROSPERO, CENTRAL, ClinicalTrials.gov, EuCTR, WHO ICTRP) and conducted online, citation, and manual searches. We assessed risks of bias across outcomes using RoB 2.0 and across studies using ROB-ME and a contour-enhanced funnel plot. (3) Results: Three RCTs were included (813 patients, both previously treated and untreated). Patients with a complete or partial response after chemotherapy were randomized to either a patient-specific recombinant idiotype keyhole limpet hemocyanin (Id-KLH) vaccine plus granulocyte–macrophage colony-stimulating factor (GM-CSF) or placebo immunotherapy (KLH + GM-CSF). Meta-analyses showed that PFS was worse with the vaccine, but not significantly: hazard ratio, 1.09 (95% CI 0.91–1.30). The GRADE certainty of evidence was moderate. Adverse event data were mixed. (4) Conclusions: We are moderately certain that Id-KLH results in little to no difference in PFS in FL. (5) Funding: Russian Science Foundation grant #22-25-00516. (6) Registration: PROSPERO CRD42023457528. Full article
(This article belongs to the Section Biopharmaceuticals)
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15 pages, 13770 KiB  
Article
Cytokine-Induced Killer Cells in Combination with Heat Shock Protein 90 Inhibitors Functioning via the Fas/FasL Axis Provides Rationale for a Potential Clinical Benefit in Burkitt’s lymphoma
by Fangfang Ge, Yulu Wang, Amit Sharma, Yu Yang, Hongde Liu, Markus Essler, Ulrich Jaehde and Ingo G. H. Schmidt-Wolf
Int. J. Mol. Sci. 2023, 24(15), 12476; https://doi.org/10.3390/ijms241512476 - 5 Aug 2023
Cited by 4 | Viewed by 2291
Abstract
Constant efforts are being made to develop methods for improving cancer immunotherapy, including cytokine-induced killer (CIK) cell therapy. Numerous heat shock protein (HSP) 90 inhibitors have been assessed for antitumor efficacy in preclinical and clinical trials, highlighting their individual prospects for targeted cancer [...] Read more.
Constant efforts are being made to develop methods for improving cancer immunotherapy, including cytokine-induced killer (CIK) cell therapy. Numerous heat shock protein (HSP) 90 inhibitors have been assessed for antitumor efficacy in preclinical and clinical trials, highlighting their individual prospects for targeted cancer therapy. Therefore, we tested the compatibility of CIK cells with HSP90 inhibitors using Burkitt’s lymphoma (BL) cells. Our analysis revealed that CIK cytotoxicity in BL cells was augmented in combination with independent HSP90 inhibitors 17-DMAG (17-dimethylaminoethylamino-17-demethoxygeldanamycin) and ganetespib. Interestingly, CIK cell cytotoxicity did not diminish after blocking with NKG2D (natural killer group 2, member D), which is a prerequisite for their activation. Subsequent analyses revealed that the increased expression of Fas on the surface of BL cells, which induces caspase 3/7-dependent apoptosis, may account for this effect. Thus, we provide evidence that CIK cells, either alone or in combination with HSP90 inhibitors, target BL cells via the Fas–FasL axis rather than the NKG2D pathway. In the context of clinical relevance, we also found that high expression of HSP90 family genes (HSP90AA1, HSP90AB1, and HSP90B1) was significantly associated with the reduced overall survival of BL patients. In addition to HSP90, genes belonging to the Hsp40, Hsp70, and Hsp110 families have also been found to be clinically significant for BL survival. Taken together, the combinatorial therapy of CIK cells with HSP90 inhibitors has the potential to provide clinical benefits to patients with BL. Full article
(This article belongs to the Section Molecular Oncology)
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29 pages, 11357 KiB  
Review
FDG-PET/CT in the Monitoring of Lymphoma Immunotherapy Response: Current Status and Future Prospects
by Akram Al-Ibraheem, Ahmed Saad Abdlkadir, Malik E. Juweid, Kamal Al-Rabi, Mohammad Ma’koseh, Hikmat Abdel-Razeq and Asem Mansour
Cancers 2023, 15(4), 1063; https://doi.org/10.3390/cancers15041063 - 7 Feb 2023
Cited by 21 | Viewed by 6809
Abstract
Cancer immunotherapy has been extensively investigated in lymphoma over the last three decades. This new treatment modality is now established as a way to manage and maintain several stages and subtypes of lymphoma. The establishment of this novel therapy has necessitated the development [...] Read more.
Cancer immunotherapy has been extensively investigated in lymphoma over the last three decades. This new treatment modality is now established as a way to manage and maintain several stages and subtypes of lymphoma. The establishment of this novel therapy has necessitated the development of new imaging response criteria to evaluate and follow up with cancer patients. Several FDG PET/CT-based response criteria have emerged to address and encompass the various most commonly observed response patterns. Many of the proposed response criteria are currently being used to evaluate and predict responses. The purpose of this review is to address the efficacy and side effects of cancer immunotherapy and to correlate this with the proposed criteria and relevant patterns of FDG PET/CT in lymphoma immunotherapy as applicable. The latest updates and future prospects in lymphoma immunotherapy, as well as PET/CT potentials, will be discussed. Full article
(This article belongs to the Special Issue PET/CT in Tumor Immunotherapy Assessment)
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15 pages, 930 KiB  
Review
Targeting Menin and CD47 to Address Unmet Needs in Acute Myeloid Leukemia
by Andrew H. Matthews, Keith W. Pratz and Martin P. Carroll
Cancers 2022, 14(23), 5906; https://doi.org/10.3390/cancers14235906 - 29 Nov 2022
Cited by 8 | Viewed by 4093
Abstract
After forty years of essentially unchanged treatment in acute myeloid leukemia (AML), innovation over the past five years has been rapid, with nine drug approvals from 2016 to 2021. Increased understanding of the molecular changes and genetic ontology of disease have led to [...] Read more.
After forty years of essentially unchanged treatment in acute myeloid leukemia (AML), innovation over the past five years has been rapid, with nine drug approvals from 2016 to 2021. Increased understanding of the molecular changes and genetic ontology of disease have led to targeting mutations in isocitrate dehydrogenase, FMS-like tyrosine kinase 3 (FLT3), B-cell lymphoma 2 and hedgehog pathways. Yet outcomes remain variable; especially in defined molecular and genetic subgroups such as NPM1 (Nucleophosmin 1) mutations, 11q23/KMT2A rearranged and TP53 mutations. Emerging therapies seek to address these unmet needs, and all three of these subgroups have promising new therapeutic approaches. Here, we will discuss the normal biological roles of menin in acute leukemia, notably in KMT2A translocations and NPM1 mutation, as well as current drug development. We will also explore how CD47 inhibition may move immunotherapy into front-line settings and unlock new treatment strategies in TP53 mutated disease. We will then consider how these new therapeutic advances may change the management of AML overall. Full article
(This article belongs to the Special Issue New Therapeutic Strategies for Acute Myeloid Leukemia)
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15 pages, 699 KiB  
Review
Targeted Therapy of B7 Family Checkpoints as an Innovative Approach to Overcome Cancer Therapy Resistance: A Review from Chemotherapy to Immunotherapy
by Bita Amir Taghavi, Nazila Alizadeh, Hossein Saeedi, Noora Karim Ahangar, Afshin Derakhshani, Khalil Hajiasgharzadeh, Nicola Silvestris, Behzad Baradaran and Oronzo Brunetti
Molecules 2022, 27(11), 3545; https://doi.org/10.3390/molecules27113545 - 31 May 2022
Cited by 7 | Viewed by 3577
Abstract
It is estimated that there were 18.1 million cancer cases worldwide in 2018, with about 9 million deaths. Proper diagnosis of cancer is essential for its effective treatment because each type of cancer requires a specific treatment procedure. Cancer therapy includes one or [...] Read more.
It is estimated that there were 18.1 million cancer cases worldwide in 2018, with about 9 million deaths. Proper diagnosis of cancer is essential for its effective treatment because each type of cancer requires a specific treatment procedure. Cancer therapy includes one or more approaches such as surgery, radiotherapy, chemotherapy, and immunotherapy. In recent years, immunotherapy has received much attention and immune checkpoint molecules have been used to treat several cancers. These molecules are involved in regulating the activity of T lymphocytes. Accumulated evidence shows that targeting immune checkpoint regulators like PD-1/PD-L1 and CTLA-4 are significantly useful in treating cancers. According to studies, these molecules also have pivotal roles in the chemoresistance of cancer cells. Considering these findings, the combination of immunotherapy and chemotherapy can help to treat cancer with a more efficient approach. Among immune checkpoint molecules, the B7 family checkpoints have been studied in various cancer types such as breast cancer, myeloma, and lymphoma. In these cancers, they cause the cells to become resistant to the chemotherapeutic agents. Discovering the exact signaling pathways and selective targeting of these checkpoint molecules may provide a promising avenue to overcome cancer development and therapy resistance. Highlights: (1) The development of resistance to cancer chemotherapy or immunotherapy is the main obstacle to improving the outcome of these anti-cancer therapies. (2) Recent investigations have described the involvement of immune checkpoint molecules in the development of cancer therapy resistance. (3) In the present study, the molecular participation of the B7 immune checkpoint family in anticancer therapies has been highlighted. (4) Targeting these immune checkpoint molecules may be considered an efficient approach to overcoming this obstacle. Full article
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28 pages, 1636 KiB  
Review
CCR4 as a Therapeutic Target for Cancer Immunotherapy
by Osamu Yoshie
Cancers 2021, 13(21), 5542; https://doi.org/10.3390/cancers13215542 - 4 Nov 2021
Cited by 74 | Viewed by 10929
Abstract
CCR4 is a chemokine receptor mainly expressed by T cells. It is the receptor for two CC chemokine ligands, CCL17 and CCL22. Originally, the expression of CCR4 was described as highly selective for helper T type 2 (Th2) cells. Later, its expression was [...] Read more.
CCR4 is a chemokine receptor mainly expressed by T cells. It is the receptor for two CC chemokine ligands, CCL17 and CCL22. Originally, the expression of CCR4 was described as highly selective for helper T type 2 (Th2) cells. Later, its expression was extended to other T cell subsets such as regulatory T (Treg) cells and Th17 cells. CCR4 has long been regarded as a potential therapeutic target for allergic diseases such as atopic dermatitis and bronchial asthma. Furthermore, the findings showing that CCR4 is strongly expressed by T cell malignancies such as adult T cell leukemia/lymphoma (ATLL) and cutaneous T cell lymphomas (CTCLs) have led to the development and clinical application of the fully humanized and glyco-engineered monoclonal anti-CCR4 Mogamulizumab in refractory/relapsed ATLL and CTCLs with remarkable successes. However, Mogamulizumab often induces severe adverse events in the skin possibly because of its efficient depletion of Treg cells. In particular, treatment with Mogamulizumab prior to allogenic hematopoietic stem cell transplantation (allo-HSCT), the only curative option of these T cell malignancies, often leads to severe glucocorticoid-refractory graft-versus-host diseases. The efficient depletion of Treg cells by Mogamulizumab has also led to its clinical trials in advanced solid tumors singly or in combination with immune checkpoint inhibitors. The main focus of this review is CCR4; its expression on normal and malignant T cells and its significance as a therapeutic target in cancer immunotherapy. Full article
(This article belongs to the Special Issue Emerging Roles of Chemokines in Cancer Immunotherapy)
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20 pages, 41659 KiB  
Article
The RXR Agonist MSU42011 Is Effective for the Treatment of Preclinical HER2+ Breast Cancer and Kras-Driven Lung Cancer
by Ana S. Leal, Jessica A. Moerland, Di Zhang, Sarah Carapellucci, Beth Lockwood, Teresa Krieger-Burke, Bilal Aleiwi, Edmund Ellsworth and Karen T. Liby
Cancers 2021, 13(19), 5004; https://doi.org/10.3390/cancers13195004 - 6 Oct 2021
Cited by 13 | Viewed by 3473
Abstract
(1) Background: Notwithstanding numerous therapeutic advances, 176,000 deaths from breast and lung cancers will occur in the United States in 2021 alone. The tumor microenvironment and its modulation by drugs have gained increasing attention and relevance, especially with the introduction of immunotherapy as [...] Read more.
(1) Background: Notwithstanding numerous therapeutic advances, 176,000 deaths from breast and lung cancers will occur in the United States in 2021 alone. The tumor microenvironment and its modulation by drugs have gained increasing attention and relevance, especially with the introduction of immunotherapy as a standard of care in clinical practice. Retinoid X receptors (RXRs) are members of the nuclear receptor superfamily and upon ligand binding, function as transcription factors to modulate multiple cell functions. Bexarotene, the only FDA-approved RXR agonist, is still used to treat cutaneous T-cell lymphoma. (2) Methods: To test the immunomodulatory and anti-tumor effects of MSU42011, a new RXR agonist, we used two different immunocompetent murine models (MMTV-Neu mice, a HER2 positive model of breast cancer and the A/J mouse model, in which vinyl carbamate is used to initiate lung tumorigenesis) and an immunodeficient xenograft lung cancer model. (3) Results: Treatment of established tumors in immunocompetent models of HER2-positive breast cancer and Kras-driven lung cancer with MSU42011 significantly decreased the tumor burden and increased the ratio of CD8/CD4, CD25 T cells, which correlates with enhanced anti-tumor efficacy. Moreover, the combination of MSU42011 and immunotherapy (anti-PDL1 and anti-PD1 antibodies) significantly (p < 0.05) reduced tumor size vs. individual treatments. However, MSU42011 was ineffective in an athymic human A549 lung cancer xenograft model, supporting an immunomodulatory mechanism of action. (4) Conclusions: Collectively, these data suggest that the RXR agonist MSU42011 can be used to modulate the tumor microenvironment in breast and lung cancer. Full article
(This article belongs to the Section Cancer Therapy)
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23 pages, 1252 KiB  
Review
Cardiac Toxicity Associated with Cancer Immunotherapy and Biological Drugs
by Andrea Montisci, Maria Teresa Vietri, Vittorio Palmieri, Silvia Sala, Francesco Donatelli and Claudio Napoli
Cancers 2021, 13(19), 4797; https://doi.org/10.3390/cancers13194797 - 25 Sep 2021
Cited by 21 | Viewed by 6634
Abstract
Cancer immunotherapy significantly contributed to an improvement in the prognosis of cancer patients. Immunotherapy, including human epidermal growth factor receptor 2 (HER2)-targeted therapies, immune checkpoint inhibitors (ICI), and chimeric antigen receptor-modified T (CAR-T), share the characteristic to exploit the capabilities of the immune [...] Read more.
Cancer immunotherapy significantly contributed to an improvement in the prognosis of cancer patients. Immunotherapy, including human epidermal growth factor receptor 2 (HER2)-targeted therapies, immune checkpoint inhibitors (ICI), and chimeric antigen receptor-modified T (CAR-T), share the characteristic to exploit the capabilities of the immune system to kill cancerous cells. Trastuzumab is a monoclonal antibody against HER2 that prevents HER2-mediated signaling; it is administered mainly in HER2-positive cancers, such as breast, colorectal, biliary tract, and non-small-cell lung cancers. Immune checkpoint inhibitors (ICI) inhibit the binding of CTLA-4 or PD-1 to PDL-1, allowing T cells to kill cancerous cells. ICI can be used in melanomas, non-small-cell lung cancer, urothelial, and head and neck cancer. There are two main types of T-cell transfer therapy: tumor-infiltrating lymphocytes (or TIL) therapy and chimeric antigen receptor-modified T (CAR-T) cell therapy, mainly applied for B-cell lymphoma and leukemia and mantle-cell lymphoma. HER2-targeted therapies, mainly trastuzumab, are associated with left ventricular dysfunction, usually reversible and rarely life-threatening. PD/PDL-1 inhibitors can cause myocarditis, rare but potentially fulminant and associated with a high fatality rate. CAR-T therapy is associated with several cardiac toxic effects, mainly in the context of a systemic adverse effect, the cytokines release syndrome. Full article
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9 pages, 1292 KiB  
Article
Evolution of Systemic Treatment Uptake and Survival in Advanced Non-Small Cell Lung Cancer
by Sophie Stock-Martineau, Katie Laurie, Mathieu McKinnon, Tinghua Zhang and Paul Wheatley-Price
Curr. Oncol. 2021, 28(1), 60-68; https://doi.org/10.3390/curroncol28010008 - 4 Dec 2020
Cited by 10 | Viewed by 3623
Abstract
Background: Non-small cell lung cancer (NSCLC) commonly presents at advanced stage. We previously reported systemic treatment uptake in stage IV NSCLC climbing from 55% (2009–2012) to 62% (2015–2017). Since then, first-line immunotherapy and 2nd/3rd generation tyrosine kinase inhibitors (TKIs) have emerged as standards [...] Read more.
Background: Non-small cell lung cancer (NSCLC) commonly presents at advanced stage. We previously reported systemic treatment uptake in stage IV NSCLC climbing from 55% (2009–2012) to 62% (2015–2017). Since then, first-line immunotherapy and 2nd/3rd generation tyrosine kinase inhibitors (TKIs) have emerged as standards of care. We explored whether treatment rates continued to rise and studied outcomes. Methods: We reviewed all cases of de novo stage IIIB/IIIC/IV NSCLC seen in out-patient medical oncology consultation at our institution between 2009–2012 (cohort A), 2015–2017 (cohort B), and June–December 2018 (cohort C). We compared rates of systemic treatment, molecular testing, targeted therapy, and immune checkpoint inhibitor (ICI) use. We compared survival in the overall, treated/untreated, younger and elderly population in cohort A vs. cohort B + C (=cohort D). Results: Cohorts A, B, and C included 528, 463, and 93 patients, respectively. Overall, 66% received any systemic therapy in cohort C, compared to 62% in cohort B and 55% in cohort A. Across three time periods, first-line chemotherapy rates fell (93, 76, 46%) while rates of first-line targeted therapy (5, 16, 15%) and ICI (0, 2, 36%) rose. Among molecular subtypes, first-line targeted treatment in EGFR-positive patients (63, 94, 100%) and anaplastic lymphoma kinase (ALK)-positive patients (0, 91, 100%) rose. Survival improved in all subgroups in cohort D vs. cohort A, except for patients ≥ 70 years and the untreated population. Conclusions: Systemic treatment rose across three time periods, reflecting the introduction of rapid diagnostic pathways, reflex molecular testing, ICI, and targeted therapies. Survival outcomes of advanced NSCLC patients have significantly improved. Full article
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16 pages, 4399 KiB  
Perspective
Synergistic Effects of Nanomedicine Targeting TNFR2 and DNA Demethylation Inhibitor—An Opportunity for Cancer Treatment
by Mohammad A. I. Al-Hatamleh, Engku Nur Syafirah E.A.R., Jennifer C. Boer, Khalid Ferji, Jean-Luc Six, Xin Chen, Eyad Elkord, Magdalena Plebanski and Rohimah Mohamud
Cells 2020, 9(1), 33; https://doi.org/10.3390/cells9010033 - 20 Dec 2019
Cited by 17 | Viewed by 5405
Abstract
Tumor necrosis factor receptor 2 (TNFR2) is expressed on some tumor cells, such as myeloma, Hodgkin lymphoma, colon cancer and ovarian cancer, as well as immunosuppressive cells. There is increasingly evidence that TNFR2 expression in cancer microenvironment has significant implications in cancer progression, [...] Read more.
Tumor necrosis factor receptor 2 (TNFR2) is expressed on some tumor cells, such as myeloma, Hodgkin lymphoma, colon cancer and ovarian cancer, as well as immunosuppressive cells. There is increasingly evidence that TNFR2 expression in cancer microenvironment has significant implications in cancer progression, metastasis and immune evasion. Although nanomedicine has been extensively studied as a carrier of cancer immunotherapeutic agents, no study to date has investigated TNFR2-targeting nanomedicine in cancer treatment. From an epigenetic perspective, previous studies indicate that DNA demethylation might be responsible for high expressions of TNFR2 in cancer models. This perspective review discusses a novel therapeutic strategy based on nanomedicine that has the capacity to target TNFR2 along with inhibition of DNA demethylation. This approach may maximize the anti-cancer potential of nanomedicine-based immunotherapy and, consequently, markedly improve the outcomes of the management of patients with malignancy. Full article
(This article belongs to the Section Cellular Immunology)
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