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Keywords = 3Es of immunotherapy

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25 pages, 7475 KiB  
Article
Human Dialyzable Leukocyte Extract Enhances Albendazole Efficacy and Promotes Th1/Th2-Biased Lymphocyte and Antibody Responses in Peritoneal Cavity of Murine Model of Mesocestoides vogae Infection
by Gabriela Hrčková, Dagmar Mudroňová, Katarína Reiterová, Serena Cavallero and Ilaria Bellini
Int. J. Mol. Sci. 2025, 26(14), 6994; https://doi.org/10.3390/ijms26146994 - 21 Jul 2025
Viewed by 273
Abstract
Human leukocyte extract (HLE), a non-immunogenic dialyzable leukocyte preparation (<10 kDa), may serve as a safe adjuvant in immunotherapy. We investigated the effects of albendazole (ABZ), HLE, and their combination in Mesocestoides vogae infected mice, focusing on lymphoid cells in the peritoneal cavity, [...] Read more.
Human leukocyte extract (HLE), a non-immunogenic dialyzable leukocyte preparation (<10 kDa), may serve as a safe adjuvant in immunotherapy. We investigated the effects of albendazole (ABZ), HLE, and their combination in Mesocestoides vogae infected mice, focusing on lymphoid cells in the peritoneal cavity, the site of larval proliferation and parasite-induced immunosuppression. Peritoneal lymphoid cells were analysed by flow cytometry and qPCR. Cells proliferative responses to ConA, LPS, and parasite excretory/secretory (E/S) antigens, cytokine production (ELISA), IgM and IgG isotypes in exudates and parasite antigen recognition (Western blot) were assessed. Efficacy was measured by larval burden and 14-3-3 gene expression in larvae. HLE combined with ABZ enhanced larval clearance and suppressed 14-3-3 gene expression in larvae. HLE and combination therapy increased CD3+ T cell frequencies, especially CD3+high, reduced regulatory CD3+/IL-10 Tregs and expression of Foxp3+. All treatments diminished CD19+/IL-10+ Bregs, correlating with lower CD9 and Atf3 mRNA levels compared to infected mice. Transcription factors T-bet expression was strongly upregulated, while GATA3 was moderately elevated. IFN-γ production and T/B cell proliferation were restored after HLE and combination therapy, partially, even in the presence of E/S antigens. IgM and total IgG levels against parasite antigens declined, while Th1-associated IgG2a increased in ABZ+HLE and HLE-treated groups. Albendazole failed to reverse the immunosuppressive Treg-type immunity but was more effective in reducing Breg populations and their functions. HLE enhanced ABZ efficacy by restoring Th1 responsiveness, reducing Treg/Breg activity, and modulating antibody profiles. It represents a promising immunomodulatory adjuvant in the treatment of the infections associated with Th2/Treg-driven immunosuppression. Full article
(This article belongs to the Special Issue Molecular Research on Parasitic Infection)
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10 pages, 674 KiB  
Article
Impact of Treatment Duration in First-Line Atezolizumab Plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer: A Multicenter Real-World Retrospective Study
by Mehmet Nuri Baser, Bilgin Demir, Gamze Serin Ozel, Gamze Gokoz Dogu, Serdar Karakaya, Mucahit Ugar, Naziye Ak, Ahmet Ozveren, Ufuk Camanlı, Olcun Umit Unal, Merve Turan and Esin Oktay
Medicina 2025, 61(7), 1230; https://doi.org/10.3390/medicina61071230 - 7 Jul 2025
Viewed by 397
Abstract
Background and Objectives: Small-cell lung cancer (SCLC) is an exceedingly aggressive neoplasm distinguished by an unfavorable prognosis. Recent studies have confirmed chemo-immunotherapy as the conventional first treatment for extensive-stage small-cell lung cancer (ES-SCLC), but the impact of treatment duration remains unclear. The goal [...] Read more.
Background and Objectives: Small-cell lung cancer (SCLC) is an exceedingly aggressive neoplasm distinguished by an unfavorable prognosis. Recent studies have confirmed chemo-immunotherapy as the conventional first treatment for extensive-stage small-cell lung cancer (ES-SCLC), but the impact of treatment duration remains unclear. The goal of this study was to find out how the length of treatment affected progression-free survival (PFS) and overall survival (OS) in patients with ES-SCLC who were receiving first-line atezolizumab plus chemotherapy. Materials and Methods: This retrospective multicenter study comprised 82 patients from six oncology centers in Turkey between 2017 and 2024. Patients were categorized into two categories according to the quantity of chemotherapy cycles they had undergone: standard treatment (≤4 cycles) and extended treatment (≥5 cycles). For the purpose of analyzing survival outcomes and related clinical determinants, as well as the demographic structures and features of the patients, both univariate and multivariate Cox regression models were utilized. Results: The median number of atezolizumab cycles was 8 (1–63). OS was 29.46 months after 15.8 months of follow-up, while PFS was 10.63 months. When comparing the two groups, we found no statistically significant differences in either PFS (p = 0.952) or OS (p = 0.374). Significant associations with OS were seen in the standard therapy group for both ECOG PS 1 (p = 0.028). Thoracic radiation considerably decreased progression risk (HR = 0.41, p = 0.031) in the extended group. Conclusions: While prolonging chemo-immunotherapy beyond four cycles did not significantly improve survival, the selected patient subgroups may benefit from personalized approaches. Thoracic radiotherapy emerged as a key modifier of outcome. Full article
(This article belongs to the Section Oncology)
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10 pages, 2360 KiB  
Case Report
The New Frontier in Small-Cell Lung Cancer: Can Atezolizumab Ensure Enduring Stability?
by Stefano Notarangelo, Renato Lombardi, Massimo Lombardi, Giovanna Liguori, Marco Taurchini, Marco Sperandeo, Leonardo Specchiulli, Paola Conte, Fabrizia Checola, Emilia Langella, Antonio Giordano, Roberto Bava and Stefano Ruga
Sci. Pharm. 2025, 93(3), 29; https://doi.org/10.3390/scipharm93030029 - 5 Jul 2025
Viewed by 453
Abstract
Small-cell lung cancer (SCLC) is an aggressive malignancy with poor prognosis despite initial responsiveness to chemotherapy. Platinum-based chemotherapy with etoposide has long been the standard first-line treatment, but recent advances in immunotherapy have improved outcomes. Phase III trials, including IMpower133 and CASPIAN, demonstrated [...] Read more.
Small-cell lung cancer (SCLC) is an aggressive malignancy with poor prognosis despite initial responsiveness to chemotherapy. Platinum-based chemotherapy with etoposide has long been the standard first-line treatment, but recent advances in immunotherapy have improved outcomes. Phase III trials, including IMpower133 and CASPIAN, demonstrated that adding immune checkpoint inhibitors, such as atezolizumab and durvalumab, to chemotherapy significantly enhances overall survival (OS) and progression-free survival (PFS). This case report describes a 76-year-old former smoker diagnosed with extensive-stage SCLC (ES-SCLC) following the detection of a left lower lung mass. The patient underwent combination therapy with carboplatin, etoposide, and atezolizumab, followed by maintenance atezolizumab. The patient demonstrated a sustained response to treatment, with significant tumor regression and no evidence of disease progression. Despite advanced age and comorbidities, treatment was well-tolerated, with no severe adverse events. Serial imaging over 24 months confirmed sustained disease stability, with regression of mediastinal lymphadenopathy and no new lesions. This case highlights the potential for prolonged disease control in select SCLC patients treated with chemo-immunotherapy. The absence of significant toxicities underscores the feasibility of immunotherapy even in elderly patients with comorbidities. These findings support the role of atezolizumab as a key component of ES-SCLC treatment and suggest the need for further research on predictors of durable response. Full article
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11 pages, 442 KiB  
Article
Lack of Prophylactic Cranial Irradiation for Extensive Small-Cell Lung Cancer in Real Life, with the Emergence of Immunotherapy
by Alice Daumas, Celestin Bigarre, Mohamed Boucekine, Audrey Zaccariotto, Bertrand Kaeppelin, Alice Mogenet, Etienne Gouton, Johan Pluvy, Pascale Tomasini, Xavier Muracciole, Sebastien Benzekry, Laurent Greillier and Laetitia Padovani
Cancers 2024, 16(23), 4122; https://doi.org/10.3390/cancers16234122 - 9 Dec 2024
Viewed by 1341
Abstract
Background: Prophylactic cranial irradiation (PCI) is recommended to decrease the incidence of brain metastases (BM) in extensive-stage small-cell lung cancer (ESSCLC) without BM after response to chemotherapy. However, PCI is associated with significant neurocognitive effects, and new studies are debating its benefits. Moreover, [...] Read more.
Background: Prophylactic cranial irradiation (PCI) is recommended to decrease the incidence of brain metastases (BM) in extensive-stage small-cell lung cancer (ESSCLC) without BM after response to chemotherapy. However, PCI is associated with significant neurocognitive effects, and new studies are debating its benefits. Moreover, the introduction of immunotherapy in the management of the disease has raised new questions, and there is a lack of data on PCI and immunotherapy. We report a single-center retrospective study evaluating the impact of omitting PCI from real-life treatment, including immunotherapy, of patients with ES-SCLC. Methods: We identified patients followed at APHM between January 2014 and January 2021 for ES-SCLC without BM with an indication for PCI. The main assessment criteria considered in this study were overall survival (OS) and brain metastasis-free survival (BMFS) between patients who received PCI and those who did not. Results: 56 patients were included, 25 receiving PCI and 31 without PCI. The median follow-up was 16 months. Eighteen patients received immunotherapy, mostly in the group without PCI (p = 0.024). The median OS and BMFS were, respectively, 11.7 and 13.4 months in patients with PCI, and 20.3 and 10.7 months in patients without PCI, without any significant statistical difference (p = 0.412, p = 0.336). The prognostic factors highlighted in multivariate analysis were initial performance status (PS) < 2 for OS (HR = 2.74 (IC95% [1.23; 6.13])) and monocyte lymphocyte ratio (MLR) < 0.12 for BMFS (HR = 1.21 (IC95% [1.01; 1.45])). A recursive partitioning analysis (RPA) found PS, immunotherapy, and age to be influential factors for OS but not PCI. Conclusions: The clinical results of our study showed no benefit of PCI in terms of OS and BMFS for patients with ES-SCLC. This can be explained by the lack of benefit of PCI or by the introduction of immunotherapy. Full article
(This article belongs to the Special Issue Educating Recent Updates on Metastatic Non-small Cell Lung Cancer)
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12 pages, 1745 KiB  
Article
Current Radiotherapy Management of Extensive-Stage Small-Cell Lung Cancer in the Immunotherapy Era: An Italian National Survey on Behalf of the Italian Association of Radiotherapy and Clinical Oncology (AIRO)
by Alessio Bruni, Vieri Scotti, Maria Alessia Zerella, Federica Bertolini, Jessica Imbrescia, Emanuela Olmetto, Chiara Bennati, Francesco Cuccia, Marianna Miele, Niccolò Giaj-Levra, Marcello Tiseo, Patrizia Ciammella, Stefano Vagge, Marco Galaverni, Antonio Pontoriero, Serena Badellino, Ruggero Spoto, Emanuele Alì and Paolo Borghetti
Curr. Oncol. 2024, 31(11), 6791-6802; https://doi.org/10.3390/curroncol31110501 - 1 Nov 2024
Cited by 1 | Viewed by 1526
Abstract
Background: Extensive-stage small-cell lung cancer (ES-SCLC) treatment has recently been revolutionized by the advent of immune checkpoint inhibitors. This survey was conducted to evaluate the current pattern of care among Italian clinicians, in particular about the integration with radiation therapy (RT). Methods: In [...] Read more.
Background: Extensive-stage small-cell lung cancer (ES-SCLC) treatment has recently been revolutionized by the advent of immune checkpoint inhibitors. This survey was conducted to evaluate the current pattern of care among Italian clinicians, in particular about the integration with radiation therapy (RT). Methods: In June 2023, 225 Italian cancer care professionals were invited to complete a 21-question web-based survey about ES-SCLC management through personal contacts and the Italian Association for Radiotherapy and Clinical Oncology (AIRO) network. Results: We received 90 responses; the majority were radiation oncologists (89%) with more than 10 years of experience (51%). The preferred management of ES-SCLC in patients with a good performance status was concomitant chemo-immunotherapy (84%). Almost all respondents recommended prophylactic cranial irradiation (PCI) (85%), taking into account age and thoracic response; PCI was performed mainly between the end of chemotherapy and before starting immunotherapy (37%), with a three-dimensional conformal technique (46%). Furthermore, 83% of respondents choose to deliver thoracic RT in the case of both an intrathoracic and extrathoracic response, with an RT schedule of 30 Gy/10 fractions. Stereotactic RT is increasingly being used in oligoprogressions. Conclusions: Our analysis showed the variability of real-world management of ES-SCLC. Future clinical trials and developments are needed to improve the multidisciplinary treatment of these patients. Full article
(This article belongs to the Special Issue Hype or Hope—Combination Therapies for Lung Cancer)
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17 pages, 4034 KiB  
Article
Comparison of Natural Killer Cells Differentiated from Various Pluripotent Stem Cells
by Jongsuk Han, Hyeongbin Son, Daun Jung, Ki-Yeon Kim, Chaeyeon Jin, Hyeonwook Hwang, Soon-Suk Kang, Shoukhrat Mitalipov, Hee-Jung An, Yeonmi Lee and Eunju Kang
Int. J. Mol. Sci. 2024, 25(15), 8209; https://doi.org/10.3390/ijms25158209 - 27 Jul 2024
Cited by 2 | Viewed by 2653
Abstract
Allogeneic natural killer (NK) cell therapy has been effective in treating cancer. Many studies have tested NK cell therapy using human pluripotent stem cells (hPSCs). However, the impacts of the origin of PSC-NK cells on competence are unclear. In this study, several types [...] Read more.
Allogeneic natural killer (NK) cell therapy has been effective in treating cancer. Many studies have tested NK cell therapy using human pluripotent stem cells (hPSCs). However, the impacts of the origin of PSC-NK cells on competence are unclear. In this study, several types of hPSCs, including human-induced PSCs (hiPSCs) generated from CD34+, CD3−CD56+, and CD56− cells in umbilical cord blood (UCB), three lines of human embryonic stem cells (hESCs, ES-1. ES-2 and ES-3) and MHC I knockout (B2M-KO)-ESCs were used to differentiate into NK cells and their capacities were analyzed. All PSC types could differentiate into NK cells. Among the iPSC-derived NK cells (iPSC-NKs) and ESC-derived NK cells (ES-NKs), 34+ iPSCs and ES-3 had a higher growth rate and cytotoxicity, respectively, ES-3 also showed better efficacy than 34+ iPSCs. B2M-KO was similar to the wild type. These results suggest that the screening for differentiation of PSCs into NK cells prior to selecting the PSC lines for the development of NK cell immunotherapy is an essential process for universal allotransplantation, including the chimeric antigen receptor (CAR). Full article
(This article belongs to the Section Molecular Biology)
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8 pages, 1220 KiB  
Case Report
Durable Response to Atezolizumab in Extensive-Stage Small-Cell Lung Cancer Leading to 60 Months Overall Survival: A Case Report
by Freeman Paczkowski, Jacques Raphael and Claire Browne
Curr. Oncol. 2024, 31(7), 3682-3689; https://doi.org/10.3390/curroncol31070271 - 27 Jun 2024
Cited by 3 | Viewed by 3836
Abstract
Small-cell lung cancer (SCLC) remains a disease with poor prognosis, particularly in extensive-stage SCLC (ES-SCLC). Current standard-of-care treatment includes chemotherapy with platinum agents and etoposide plus immunotherapy with atezolizumab or durvalumab, which has achieved a mean overall survival of 12–13 months in clinical [...] Read more.
Small-cell lung cancer (SCLC) remains a disease with poor prognosis, particularly in extensive-stage SCLC (ES-SCLC). Current standard-of-care treatment includes chemotherapy with platinum agents and etoposide plus immunotherapy with atezolizumab or durvalumab, which has achieved a mean overall survival of 12–13 months in clinical trials. However, long-term survival in ES-SCLC, even with the addition of immunotherapy, continues to be rare. We present the case of a middle-aged male patient diagnosed with ES-SCLC who was treated with four cycles of induction chemotherapy (carboplatin and etoposide) and atezolizumab, starting maintenance atezolizumab every 21 days thereafter, and thoracic radiotherapy. After 9 months, he experienced mild disease progression and was rechallenged with six cycles of carboplatin and etoposide with continued atezolizumab. Subsequent imaging showed near-complete disease resolution which has been sustained since. He has continued on maintenance atezolizumab since diagnosis and has achieved 60 months overall survival and 44 months progression-free survival. Throughout treatment, he has maintained a high functional capacity and only experienced one immune-related adverse event. Our patient is representative of a small subset who are capable of achieving durable responses to immunotherapy and his case highlights the need for further research to elucidate the clinical and biological factors driving this response. Full article
(This article belongs to the Section Thoracic Oncology)
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15 pages, 1087 KiB  
Article
Early-Stage Non-Small Cell Lung Cancer: Prevalence of Actionable Alterations in a Monocentric Consecutive Cohort
by Rossella Bruno, Anello Marcello Poma, Martina Panozzi, Alessandra Lenzini, Gianmarco Elia, Carmelina Cristina Zirafa, Vittorio Aprile, Marcello Carlo Ambrogi, Editta Baldini, Marco Lucchi, Franca Melfi, Antonio Chella, Andrea Sbrana and Greta Alì
Cancers 2024, 16(7), 1410; https://doi.org/10.3390/cancers16071410 - 3 Apr 2024
Cited by 7 | Viewed by 3693
Abstract
Early-stage (ES) non-small cell lung cancer (NSCLC) is diagnosed in about 30% of cases. The preferred treatment is surgery, but a significant proportion of patients experience recurrence. Neoadjuvant and adjuvant chemotherapy has a limited clinical benefit. EGFR tyrosine kinase inhibitors and immunotherapy have [...] Read more.
Early-stage (ES) non-small cell lung cancer (NSCLC) is diagnosed in about 30% of cases. The preferred treatment is surgery, but a significant proportion of patients experience recurrence. Neoadjuvant and adjuvant chemotherapy has a limited clinical benefit. EGFR tyrosine kinase inhibitors and immunotherapy have recently opened new therapeutic scenarios. However, only a few data are available about the ES-NSCLC molecular landscape and the impact of oncogene addiction on therapy definition. Here, we determined the prevalence of the main lung cancer driver alterations in a monocentric consecutive cohort. Molecular analysis was performed on 1122 cases, including 368 ES and 754 advanced NSCLC. The prevalence of actionable alterations was similar between early and advanced stages. ES-NSCLC was significantly enriched for MET exon-14 skipping alterations and presented a lower prevalence of BRAF p.(V600E) mutation. PD-L1 expression levels, evaluated according to actionable alterations, were higher in advanced than early tumors harboring EGFR, KRAS, MET alterations and gene fusions. Taken together, these results confirm the value of biomarker testing in ES-NSCLC. Although approved targeted therapies for ES-NSCLC are still limited, the identification of actionable alterations could improve patients’ selection for immunotherapy, favoring the enrollment in clinical trials and allowing a faster treatment start at disease recurrence. Full article
(This article belongs to the Section Cancer Biomarkers)
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13 pages, 816 KiB  
Article
A Systemic Immune Inflammation Index and PD-L1 (SP142) Expression as a Potential Combined Biomarker of the Clinical Benefit of Chemo-Immunotherapy in Extensive-Stage Small-Cell Lung Cancer
by Jong-Min Baek, Hyungkeun Cha, Yeonsook Moon, Lucia Kim, Seung Min Kwak, Eun Sun Park and Hae-Seong Nam
J. Clin. Med. 2024, 13(5), 1521; https://doi.org/10.3390/jcm13051521 - 6 Mar 2024
Cited by 4 | Viewed by 2058
Abstract
Background: No studies have identified combined biomarkers that may be more reasonable for the assessment of current chemo-immunotherapy in patients with extensive stage small-cell lung cancer (ES-SCLC). Methods: This study was conducted to investigate a combined biomarker with prognostic or predictive [...] Read more.
Background: No studies have identified combined biomarkers that may be more reasonable for the assessment of current chemo-immunotherapy in patients with extensive stage small-cell lung cancer (ES-SCLC). Methods: This study was conducted to investigate a combined biomarker with prognostic or predictive value in ES-SCLC. We determined the best independent prognostic biomarker among the four complete blood-count-derived inflammatory biomarkers (CBC-IBs). Subsequently, we analyzed the prognostic or predictive value of combining this independent CBC-IB with PD-L1 (SP142) expression. We prospectively assessed the SP142 analyses in tumor samples at diagnosis. Results: All in all, 55 patients with ES-SCLC were classified into four groups according to the systemic immune inflammation index (SII) (low/high) and SP142 (positive/negative). The best survival was observed in the low-SII/ SP142-positive group, whereas the worst survival was observed in the high-SII/SP142-negative group (p = 0.002). The combined SII-SP142 biomarker was better for predicting both survival and disease progression in patients with ES-SCLC. Conclusions: The combined SII-SP142 biomarker can be readily and universally obtained at a low cost in clinical practice, without requiring advanced genomics technology or specialized expertise. Although further studies are needed to confirm that the combined SII-SP142 biomarker is widely applicable, it should help clinicians to identify the best patients for combined chemotherapy with atezolizumab in ES-SCLC. Full article
(This article belongs to the Special Issue Clinical Applications of Tumor Immunotherapy)
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11 pages, 1982 KiB  
Article
ES-SCLC Patients with PD-L1+ CTCs and High Percentages of CD8+PD-1+T Cells in Circulation Benefit from Front-Line Immunotherapy Treatment
by Anastasia Xagara, Argyro Roumeliotou, Alexandros Kokkalis, Konstantinos Tsapakidis, Dimitris Papakonstantinou, Vassilis Papadopoulos, Ioannis Samaras, Evagelia Chantzara, Galatea Kallergi and Athanasios Kotsakis
Biomedicines 2024, 12(1), 146; https://doi.org/10.3390/biomedicines12010146 - 10 Jan 2024
Cited by 3 | Viewed by 2313
Abstract
SCLC is an aggressive cancer type with high metastatic potential and bad prognosis. CTCs are a valuable source of tumor cells in blood circulation and are among the major contributors to metastasis. In this study we evaluated the number of CTCs that express [...] Read more.
SCLC is an aggressive cancer type with high metastatic potential and bad prognosis. CTCs are a valuable source of tumor cells in blood circulation and are among the major contributors to metastasis. In this study we evaluated the number of CTCs that express PD-L1 in treatment-naïve ES-SCLC patients receiving ICI in a front-line setting. Moreover, we explored the percentages of different immune T-cell subsets in circulation to assess their potential role in predicting responses. A total of 43 patients were enrolled—6 of them with LS-SCLC, and 37 with ES-SCLC disease. In addition, PBMCs from 10 healthy donors were used as a control group. Different T-cell subtypes were examined through multicolor FACS analysis and patients’ CTCs were detected using immunofluorescence staining. SCLC patients had higher percentages of PD-1-expressing CD3+CD4+ and CD3+CD8+ T-cells, as well as elevated PD-1 protein expression compared to healthy individuals. Additionally, in ES-SCLC patients, a positive correlation between CD3+CD8+PD-1+ T-cells and PD-L1+ CTCs was detected. Importantly, patients harboring higher numbers of CD3+CD8+PD-1+ T-cells together with PD-L1+CTCs had a survival advantage when receiving front-line immunotherapy. Thus, this study proposes, for first time possible, immune cell–CTCs interaction, as well as a potential novel clinical biomarker for ICI responses in ES-SCLC patients. Full article
(This article belongs to the Special Issue The Biology of Circulating Tumor Cells 2.0)
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18 pages, 739 KiB  
Review
Perspectives of Proteomics in Respiratory Allergic Diseases
by Miguel Ángel Galván-Morales
Int. J. Mol. Sci. 2023, 24(16), 12924; https://doi.org/10.3390/ijms241612924 - 18 Aug 2023
Cited by 1 | Viewed by 2191
Abstract
Proteomics in respiratory allergic diseases has such a battery of techniques and programs that one would almost think there is nothing impossible to find, invent or mold. All the resources that we document here are involved in solving problems in allergic diseases, both [...] Read more.
Proteomics in respiratory allergic diseases has such a battery of techniques and programs that one would almost think there is nothing impossible to find, invent or mold. All the resources that we document here are involved in solving problems in allergic diseases, both diagnostic and prognostic treatment, and immunotherapy development. The main perspectives, according to this version, are in three strands and/or a lockout immunological system: (1) Blocking the diapedesis of the cells involved, (2) Modifications and blocking of paratopes and epitopes being understood by modifications to antibodies, antagonisms, or blocking them, and (3) Blocking FcεRI high-affinity receptors to prevent specific IgEs from sticking to mast cells and basophils. These tools and targets in the allergic landscape are, in our view, the prospects in the field. However, there are still many allergens to identify, including some homologies between allergens and cross-reactions, through the identification of structures and epitopes. The current vision of using proteomics for this purpose remains a constant; this is also true for the basis of diagnostic and controlled systems for immunotherapy. Ours is an open proposal to use this vision for treatment. Full article
(This article belongs to the Collection Feature Papers in Molecular Informatics)
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18 pages, 4770 KiB  
Article
Staphylococcal Enterotoxin C2 Mutant-Induced Antitumor Immune Response Is Controlled by CDC42/MLC2-Mediated Tumor Cell Stiffness
by Xuanhe Fu, Mingkai Xu, Zhixiong Yu, Wu Gu, Zhichun Zhang, Bowen Zhang, Xiujuan Wang, Zhencheng Su and Chenggang Zhang
Int. J. Mol. Sci. 2023, 24(14), 11796; https://doi.org/10.3390/ijms241411796 - 22 Jul 2023
Viewed by 1859
Abstract
As a biological macromolecule, the superantigen staphylococcal enterotoxin C2 (SEC2) is one of the most potent known T-cell activators, and it induces massive cytotoxic granule production. With this property, SEC2 and its mutants are widely regarded as immunomodulating agents for cancer therapy. In [...] Read more.
As a biological macromolecule, the superantigen staphylococcal enterotoxin C2 (SEC2) is one of the most potent known T-cell activators, and it induces massive cytotoxic granule production. With this property, SEC2 and its mutants are widely regarded as immunomodulating agents for cancer therapy. In a previous study, we constructed an MHC-II-independent mutant of SEC2, named ST-4, which exhibits enhanced immunocyte stimulation and antitumor activity. However, tumor cells have different degrees of sensitivity to SEC2/ST-4. The mechanisms of immune resistance to SEs in cancer cells have not been investigated. Herein, we show that ST-4 could activate more powerful human lymphocyte granule-based cytotoxicity than SEC2. The results of RNA-seq and atomic force microscopy (AFM) analysis showed that, compared with SKOV3 cells, the softer ES-2 cells could escape from SEC2/ST-4-induced cytotoxic T-cell-mediated apoptosis by regulating cell softness through the CDC42/MLC2 pathway. Conversely, after enhancing the stiffness of cancer cells by a nonmuscle myosin-II-specific inhibitor, SEC2/ST-4 exhibited a significant antitumor effect against ES-2 cells by promoting perforin-dependent apoptosis and the S-phase arrest. Taken together, these data suggest that cell stiffness could be a key factor of resistance to SEs in ovarian cancer, and our findings may provide new insight for SE-based tumor immunotherapy. Full article
(This article belongs to the Section Molecular Immunology)
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15 pages, 2152 KiB  
Article
Real-World Efficacy and Safety of Thoracic Radiotherapy after First-Line Chemo-Immunotherapy in Extensive-Stage Small-Cell Lung Cancer
by Zhaoliang Xie, Jingru Liu, Min Wu, Xiaohan Wang, Yuhan Lu, Chunyan Han, Lei Cong, Jisheng Li and Xue Meng
J. Clin. Med. 2023, 12(11), 3828; https://doi.org/10.3390/jcm12113828 - 2 Jun 2023
Cited by 18 | Viewed by 2756
Abstract
(1) Background: At present, the efficacy and safety of thoracic radiotherapy (TRT) after chemo-immunotherapy (CT-IT) in patients with extensive-stage small-cell lung cancer (ES-SCLC) still remain unclear. The purpose of this study was to evaluate the role of TRT after CT-IT in patients with [...] Read more.
(1) Background: At present, the efficacy and safety of thoracic radiotherapy (TRT) after chemo-immunotherapy (CT-IT) in patients with extensive-stage small-cell lung cancer (ES-SCLC) still remain unclear. The purpose of this study was to evaluate the role of TRT after CT-IT in patients with ES-SCLC. (2) Methods: From January 2020 to October 2021, patients with ES-SCLC treated with first-line anti-PD-L1 antibody plus platinum-etoposide chemotherapy were enrolled retrospectively. The survival data and adverse events data of patients treated with or without TRT after CT-IT were collected for analysis. (3) Results: A total of 118 patients with ES-SCLC treated with first-line CT-IT were retrospectively enrolled, with 45 patients with TRT and 73 patients without TRT after CT-IT. The median PFS and OS in the CT-IT + TRT group and CT-IT only group were 8.0 months versus 5.9 months (HR = 0.64, p = 0.025) and 22.7 months versus 14.7 months (HR = 0.52, p = 0.015), respectively. The median PFS and OS in all 118 patients treated with first-line CT-IT were 7.2 and 19.8 months with an ORR of 72.0%. In multivariate analyses, liver metastasis and response to CT-IT were shown to be independent prognostic factors of PFS (p < 0.05), while liver metastasis and bone metastasis were independent predictive factors of OS (p < 0.05). Although TRT was significantly associated with better PFS and OS in univariate analysis, the association of TRT and OS failed to reach statistical significance (HR = 0.564, p = 0.052) in multivariate analysis. There was no significant difference in adverse events (AEs) between two treatment groups (p = 0.58). (4) Conclusions: ES-SCLC patients treated with TRT after first-line CT-IT had prolonged PFS and OS with an acceptable safety profile. Further prospective randomized studies are necessary to explore the efficacy and safety of this treatment modality for ES-SCLC in future. Full article
(This article belongs to the Section Respiratory Medicine)
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15 pages, 2839 KiB  
Article
Wart-Treatment Efficacy Prediction Using a CMA-ES-Based Dendritic Neuron Model
by Shuangbao Song, Botao Zhang, Xingqian Chen, Qiang Xu and Jia Qu
Appl. Sci. 2023, 13(11), 6542; https://doi.org/10.3390/app13116542 - 27 May 2023
Cited by 3 | Viewed by 1697
Abstract
Warts are a prevalent condition worldwide, affecting approximately 10% of the global population. In this study, a machine learning method based on a dendritic neuron model is proposed for wart-treatment efficacy prediction. To prevent premature convergence and improve the interpretability of the model [...] Read more.
Warts are a prevalent condition worldwide, affecting approximately 10% of the global population. In this study, a machine learning method based on a dendritic neuron model is proposed for wart-treatment efficacy prediction. To prevent premature convergence and improve the interpretability of the model training process, an effective heuristic algorithm, i.e., the covariance matrix adaptation evolution strategy (CMA-ES), is incorporated as the training method of the dendritic neuron model. Two common datasets of wart-treatment efficacy, i.e., the cryotherapy dataset and the immunotherapy dataset, are used to verify the effectiveness of the proposed method. The proposed CMA-ES-based dendritic neuron model achieves promising results, with average classification accuracies of 0.9012 and 0.8654 on the two datasets, respectively. The experimental results indicate that the proposed method achieves better or more competitive prediction results than six common machine learning models. In addition, the trained dendritic neuron model can be simplified using a dendritic pruning mechanism. Finally, an effective wart-treatment efficacy prediction method based on a dendritic neuron model, which can provide decision support for physicians, is proposed in this paper. Full article
(This article belongs to the Special Issue Machine Learning and Big Data Processing in Medical Decision Making)
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10 pages, 1736 KiB  
Systematic Review
PD-L1 Expression in Cutaneous Angiosarcomas: A Systematic Review with Meta-Analysis
by Renato Lobrano, Panagiotis Paliogiannis, Angelo Zinellu, Giuseppe Palmieri, Ivana Persico, Arduino A. Mangoni and Antonio Cossu
Curr. Oncol. 2023, 30(5), 5135-5144; https://doi.org/10.3390/curroncol30050388 - 17 May 2023
Cited by 5 | Viewed by 2485
Abstract
Cutaneous angiosarcoma (CAS) is the most common type of angiosarcoma that predominantly affects older Caucasians. The outcomes of immunotherapy in CAS are currently under investigation in relation to the expression of programmed death ligand 1 (PD-L1) and other biomarkers. We performed a systematic [...] Read more.
Cutaneous angiosarcoma (CAS) is the most common type of angiosarcoma that predominantly affects older Caucasians. The outcomes of immunotherapy in CAS are currently under investigation in relation to the expression of programmed death ligand 1 (PD-L1) and other biomarkers. We performed a systematic review and metanalysis of data from the current literature reporting on PD-L1 immunohistochemistry expression. A systematic search of publications in the electronic databases PubMed, Web of Science, and Scopus was conducted using the following terms: “PD-L1” and “angiosarcomas”. A total of ten studies reporting on 279 cases were identified and included in the meta-analysis. The pooled prevalence of PD-L1 expression in CAS was 54% (95% CI 36–71%), with high heterogeneity (I2 = 84.81%, p < 0.001). In sub-group analysis, the proportion of PD-L1 expression in CAS was significantly (p = 0.049) lower in Asian studies (ES = 35%, 95% CI 28–42%, I2 = 0.0%, p = 0.46) than in European studies (ES = 71%, 95% CI 51–89%, I2 = 48.91%, p = 0.12). Full article
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