Cancers Precision Immunotherapy
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Editor
Topical Collection Information
Dear Colleagues,
Precision immunotherapy refers to the field of matching immune therapies to a tumor's immunomic landscape in order for that tumor to be treated with immunotherapy in a "precise" manner. Because the immune environment of each tumor may be distinct, treating precisely appears to require a personalized/individualized immunotherapy approach. There are many innovative ways to address the immune deficits that allow tumors to grow. Some of the new and powerful tools in the therapeutic armamentarium include CAR T-cells, bispecific antibodies, personalized vaccines, immune checkpoint inhibitors and immune stimulatory molecules. Interrogating the tumor immunogram and matching the patient to the compounds that are most likely to reactivate the immune system and permit it to eliminate cancer cells requires multiple advanced molecular technologies. Even so, precision immunotherapy has shown a remarkable ability to eradicate even advanced malignancies.
Prof. Dr. Razelle Kurzrock
Guest Editor
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Keywords
- immunotherapy
- checkpoint blockade
- CAR T cells
- bispecific antibodies
- personalized vaccines
Published Papers (6 papers)
Open AccessArticle
Retrospective Analysis of HLA Class II-Restricted Neoantigen Peptide-Pulsed Dendritic Cell Vaccine for Breast Cancer
by
Takafumi Morisaki, Makoto Kubo, Shinji Morisaki, Masayo Umebayashi, Hiroto Tanaka, Norihiro Koya, Shinichiro Nakagawa, Kenta Tsujimura, Sachiko Yoshimura, Kazuma Kiyotani, Yusuke Nakamura, Masafumi Nakamura and Takashi Morisaki
Viewed by 600
Abstract
Background/Objectives: Neoantigens have attracted attention as ideal therapeutic targets for anti-tumour immunotherapy because the T cells that respond to neoantigens are not affected by central immune tolerance. Recent findings have revealed that the activation of CD4-positive T cells plays a central role
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Background/Objectives: Neoantigens have attracted attention as ideal therapeutic targets for anti-tumour immunotherapy because the T cells that respond to neoantigens are not affected by central immune tolerance. Recent findings have revealed that the activation of CD4-positive T cells plays a central role in antitumor immunity, and thus targeting human leukocyte antigen (HLA) class II-restricted neoantigens, which are targets of CD4-positive T cells, is of significance. However, there are very few detailed reports of neoantigen vaccine therapies that use an HLA class II-restricted long peptide. In the present study, we retrospectively analysed the ability of HLA class II-restricted neoantigen-pulsed dendritic cell vaccines to induce immune response in five breast cancer patients.
Methods: We performed whole exome and RNA sequencing of breast cancer tissues and neoantigen prediction using an in silico pipeline. We then administered dendritic cells pulsed with synthesized an HLA class II-restricted long peptide containing an epitope with high affinity to HLA class I in the lymph node.
Results: ELISPOT analysis confirmed that a T-cell response specific for the HLA class II-restricted neoantigen was induced in all cases. TCR repertoire analysis of peripheral blood mononuclear cells before and after treatment in three patients showed increases of specific T-cell clones in two of the three patients. Importantly, no recurrence was observed in all patients.
Conclusions: Our analysis demonstrated the immunological efficacy of the HLA class II-restricted neoantigen peptide dendritic cell vaccine against breast cancer and provides useful information for the development of neoantigen vaccine therapy for breast cancer.
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Open AccessArticle
Inflammation and Immunity Gene Expression Patterns and Machine Learning Approaches in Association with Response to Immune-Checkpoint Inhibitors-Based Treatments in Clear-Cell Renal Carcinoma
by
Nikolas Dovrolis, Hector Katifelis, Stamatiki Grammatikaki, Roubini Zakopoulou, Aristotelis Bamias, Michalis V. Karamouzis, Kyriakos Souliotis and Maria Gazouli
Cited by 2 | Viewed by 1957
Abstract
Clear cell renal cell carcinoma (ccRCC) is the most common renal cancer. Despite the rapid evolution of targeted therapies, immunotherapy with checkpoint inhibition (ICI) as well as combination therapies, the cure of metastatic ccRCC (mccRCC) is infrequent, while the optimal use of the
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Clear cell renal cell carcinoma (ccRCC) is the most common renal cancer. Despite the rapid evolution of targeted therapies, immunotherapy with checkpoint inhibition (ICI) as well as combination therapies, the cure of metastatic ccRCC (mccRCC) is infrequent, while the optimal use of the various novel agents has not been fully clarified. With the different treatment options, there is an essential need to identify biomarkers to predict therapeutic efficacy and thus optimize therapeutic approaches. This study seeks to explore the diversity in mRNA expression profiles of inflammation and immunity-related circulating genes for the development of biomarkers that could predict the effectiveness of immunotherapy-based treatments using ICIs for individuals with mccRCC. Gene mRNA expression was tested by the RT2 profiler PCR Array on a human cancer inflammation and immunity crosstalk kit and analyzed for differential gene expression along with a machine learning approach for sample classification. A number of mRNAs were found to be differentially expressed in mccRCC with a clinical benefit from treatment compared to those who progressed. Our results indicate that gene expression can classify these samples with high accuracy and specificity.
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Open AccessReview
Post-Translational Modifications in Tumor-Associated Antigens as a Platform for Novel Immuno-Oncology Therapies
by
Anurag Kumar Srivastava, Giorgia Guadagnin, Paola Cappello and Francesco Novelli
Cited by 20 | Viewed by 4591
Abstract
Post-translational modifications (PTMs) are generated by adding small chemical groups to amino acid residues after the translation of proteins. Many PTMs have been reported to correlate with tumor progression, growth, and survival by modifying the normal functions of the protein in tumor cells.
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Post-translational modifications (PTMs) are generated by adding small chemical groups to amino acid residues after the translation of proteins. Many PTMs have been reported to correlate with tumor progression, growth, and survival by modifying the normal functions of the protein in tumor cells. PTMs can also elicit humoral and cellular immune responses, making them attractive targets for cancer immunotherapy. This review will discuss how the acetylation, citrullination, and phosphorylation of proteins expressed by tumor cells render the corresponding tumor-associated antigen more antigenic and affect the immune response in multiple cancers. In addition, the role of glycosylated protein mucins in anti-cancer immunotherapy will be considered. Mucin peptides in combination with stimulating adjuvants have, in fact, been utilized to produce anti-tumor antibodies and vaccines. Finally, we will also outline the results of the clinical trial exploiting glycosylated-MUC1 as a vaccine in different cancers. Overall, PTMs in TAAs could be considered in future therapies to result in lasting anti-tumor responses.
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Open AccessFeature PaperReview
Bone Marrow Immune Microenvironment in Myelodysplastic Syndromes
by
Olga Kouroukli, Argiris Symeonidis, Periklis Foukas, Myrto-Kalliopi Maragkou and Eleni P. Kourea
Cited by 17 | Viewed by 3446
Abstract
The BM, the major hematopoietic organ in humans, consists of a pleiomorphic environment of cellular, extracellular, and bioactive compounds with continuous and complex interactions between them, leading to the formation of mature blood cells found in the peripheral circulation. Systemic and local inflammation
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The BM, the major hematopoietic organ in humans, consists of a pleiomorphic environment of cellular, extracellular, and bioactive compounds with continuous and complex interactions between them, leading to the formation of mature blood cells found in the peripheral circulation. Systemic and local inflammation in the BM elicit stress hematopoiesis and drive hematopoietic stem cells (HSCs) out of their quiescent state, as part of a protective pathophysiologic process. However, sustained chronic inflammation impairs HSC function, favors mutagenesis, and predisposes the development of hematologic malignancies, such as myelodysplastic syndromes (MDS). Apart from intrinsic cellular mechanisms, various extrinsic factors of the BM immune microenvironment (IME) emerge as potential determinants of disease initiation and evolution. In MDS, the IME is reprogrammed, initially to prevent the development, but ultimately to support and provide a survival advantage to the dysplastic clone. Specific cellular elements, such as myeloid-derived suppressor cells (MDSCs) are recruited to support and enhance clonal expansion. The immune-mediated inhibition of normal hematopoiesis contributes to peripheral cytopenias of MDS patients, while immunosuppression in late-stage MDS enables immune evasion and disease progression towards acute myeloid leukemia (AML). In this review, we aim to elucidate the role of the mediators of immune response in the initial pathogenesis of MDS and the evolution of the disease.
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Open AccessReview
The Immune Contexture of Liposarcoma and Its Clinical Implications
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Antonia Resag, Giulia Toffanin, Iva Benešová, Luise Müller, Vlatko Potkrajcic, Andrej Ozaniak, Robert Lischke, Jirina Bartunkova, Antonio Rosato, Korinna Jöhrens, Franziska Eckert, Zuzana Strizova and Marc Schmitz
Cited by 11 | Viewed by 5461
Abstract
Liposarcomas (LPS) are the most frequent malignancies in the soft tissue sarcoma family and consist of five distinctive histological subtypes, termed well-differentiated LPS, dedifferentiated LPS (DDLPS), myxoid LPS (MLPS), pleomorphic LPS, and myxoid pleomorphic LPS. They display variations in genetic alterations, clinical behavior,
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Liposarcomas (LPS) are the most frequent malignancies in the soft tissue sarcoma family and consist of five distinctive histological subtypes, termed well-differentiated LPS, dedifferentiated LPS (DDLPS), myxoid LPS (MLPS), pleomorphic LPS, and myxoid pleomorphic LPS. They display variations in genetic alterations, clinical behavior, and prognostic course. While accumulating evidence implicates a crucial role of the tumor immune contexture in shaping the response to anticancer treatments, the immunological landscape of LPS is highly variable across different subtypes. Thus, DDLPS is characterized by a higher abundance of infiltrating T cells, yet the opposite was reported for MLPS. Interestingly, a recent study indicated that the frequency of pre-existing T cells in soft tissue sarcomas has a predictive value for immune checkpoint inhibitor (CPI) therapy. Additionally, B cells and tertiary lymphoid structures were identified as potential biomarkers for the clinical outcome of LPS patients and response to CPI therapy. Furthermore, it was demonstrated that macrophages, predominantly of M2 polarization, are frequently associated with poor prognosis. An improved understanding of the complex LPS immune contexture enables the design and refinement of novel immunotherapeutic approaches. Here, we summarize recent studies focusing on the clinicopathological, genetic, and immunological determinants of LPS.
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Open AccessArticle
Defining the Immune Checkpoint Landscape in Human Colorectal Cancer Highlights the Relevance of the TIGIT/CD155 Axis for Optimizing Immunotherapy
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Kathleen Ducoin, Linda Bilonda-Mutala, Cécile Deleine, Romain Oger, Emilie Duchalais, Nicolas Jouand, Céline Bossard, Anne Jarry and Nadine Gervois-Segain
Cited by 5 | Viewed by 2746
Abstract
While immune checkpoint (IC) therapies, particularly those targeting the PD-1/PD-L1 axis, have revolutionized the treatment of melanoma and several other cancers, their effect remains very limited in colorectal cancer (CRC). To define a comprehensive landscape of ICs in the human CRC tumor microenvironment
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While immune checkpoint (IC) therapies, particularly those targeting the PD-1/PD-L1 axis, have revolutionized the treatment of melanoma and several other cancers, their effect remains very limited in colorectal cancer (CRC). To define a comprehensive landscape of ICs in the human CRC tumor microenvironment (TME), we evaluated, using multiparametric flow cytometry, their ex vivo expression via tumor-infiltrating lymphocytes (TILs) (n = 40 CRCs) as well as that of their respective ligands on tumor and myeloid cells (n = 29). Supervised flow cytometry analyses showed that (i) most CD3
+ TILs expressed PD-1 and TIGIT and, to a lesser extent, Tim-3, Lag3 and NKG2A, and (ii) EpCAM
+ tumor cells and CD11b
+ myeloid cells differed in their IC ligand expression profile, with a strikingly high expression of CD155 by tumor cells. An in situ analysis of IC and their ligands using immunohistochemistry on paraffin sections of CRC confirmed the overexpression of TIGIT and its ligand, CD155, in the TME. Most interestingly, an unsupervised clustering analysis of IC co-expression on CD4
+ and CD8
+ TILs identified two tumor subgroups, named IC
high and IC
low. Altogether, our findings highlight the TIGIT/CD155 axis as a potential target that could be used in combination IC therapy in CRC.
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