Neoantigens: promising targets for cancer therapy

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Jan. 6, 2023

Abstract Recent advances in neoantigen research have accelerated the development and regulatory approval of tumor immunotherapies, including cancer vaccines, adoptive cell therapy antibody-based therapies, especially for solid tumors. Neoantigens are newly formed antigens generated by cells as a result various tumor-specific alterations, such genomic mutation, dysregulated RNA splicing, disordered post-translational modification, integrated viral open reading frames. recognized non-self trigger an immune response that is not subject to central peripheral tolerance. The quick identification prediction neoantigens been made possible advanced next-generation sequencing bioinformatic technologies. Compared tumor-associated antigens, highly immunogenic provide emerging targets personalized serve prospective predictors survival prognosis checkpoint blockade responses. therapies will be aided understanding mechanism underlying neoantigen-induced anti-tumor streamlining process neoantigen-based immunotherapies. This review provides overview on characterization outlines clinical applications immunotherapeutic strategies based neoantigens. We also explore their current status, inherent challenges, translation potential.

Language: Английский

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Therapeutic targets and biomarkers of tumor immunotherapy: response versus non-response

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: Sept. 19, 2022

Abstract Cancers are highly complex diseases that characterized by not only the overgrowth of malignant cells but also an altered immune response. The inhibition and reprogramming system play critical roles in tumor initiation progression. Immunotherapy aims to reactivate antitumor overcome escape mechanisms tumors. Represented checkpoint blockade adoptive cell transfer, immunotherapy has seen tremendous success clinic, with capability induce long-term regression some tumors refractory all other treatments. Among them, blocking therapy, represented PD-1/PD-L1 inhibitors (nivolumab) CTLA-4 (ipilimumab), shown encouraging therapeutic effects treatment various tumors, such as non-small lung cancer (NSCLC) melanoma. In addition, advent CAR-T, CAR-M novel methods, entered a new era. At present, evidence indicates combination multiple methods may be one way improve effect. However, overall clinical response rate still needs improvement, which warrants development designs well discovery biomarkers can guide prescription these agents. Learning from past failure both basic research is for rational design studies future. this article, we describe efforts manipulate against discuss different targets types exploited promote

Language: Английский

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Ovarian Cancer Immunotherapy and Personalized Medicine

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(12), P. 6532 - 6532

Published: June 18, 2021

Ovarian cancer response to immunotherapy is limited; however, the evaluation of sensitive/resistant target treatment subpopulations based on stratification by tumor biomarkers may improve predictiveness immunotherapy. These markers include mutation burden, PD-L1, tumor-infiltrating lymphocytes, homologous recombination deficiency, and neoantigen intratumoral heterogeneity. Future directions in ovarian utilization these select ideal candidates. This paper reviews role as well novel therapeutics study designs involving that increase likelihood success with cancer.

Language: Английский

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Dynamics and specificities of T cells in cancer immunotherapy

Nature reviews. Cancer, Journal Year: 2023, Volume and Issue: 23(5), P. 295 - 316

Published: April 12, 2023

Language: Английский

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Multiplexed 3D atlas of state transitions and immune interaction in colorectal cancer

Cell, Journal Year: 2023, Volume and Issue: 186(2), P. 363 - 381.e19

Published: Jan. 1, 2023

Advanced solid cancers are complex assemblies of tumor, immune, and stromal cells characterized by high intratumoral variation. We use highly multiplexed tissue imaging, 3D reconstruction, spatial statistics, machine learning to identify cell types states underlying morphological features known diagnostic prognostic significance in colorectal cancer. Quantitation these high-plex marker space reveals recurrent transitions from one tumor morphology the next, some which coincident with long-range gradients expression oncogenes epigenetic regulators. At invasive margin, where normal, immune compete, T suppression involves multiple imaging shows that seemingly localized 2D such as tertiary lymphoid structures commonly interconnected have graded molecular properties. Thus, while cancer genetics emphasizes importance discrete changes state, whole-specimen large-scale analogous those developing tissues.

Language: Английский

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Mechanisms of immune activation and regulation: lessons from melanoma

Nature reviews. Cancer, Journal Year: 2022, Volume and Issue: 22(4), P. 195 - 207

Published: Feb. 1, 2022

Language: Английский

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Functional Th1-oriented T follicular helper cells that infiltrate human breast cancer promote effective adaptive immunity

Journal of Clinical Investigation, Journal Year: 2021, Volume and Issue: 131(19)

Published: Aug. 19, 2021

We previously demonstrated that tumor-infiltrating lymphocytes (TIL) in human breast cancer sometimes form organized tertiary lymphoid structures (TLS) characterized by CXCL13-producing T follicular helper (Tfh) cells. The present study found CD4+ Tfh TIL, CD8+ and TIL-B, colocalizing TLS, all express the CXCL13 receptor CXCR5. An ex vivo functional assay determined only activated, Th1-oriented TIL (PD-1hiICOSint phenotype) provide help for immunoglobulin IFN-γ production. A presence signals an active humoral (immunoglobulins, Ki-67+ TIL-B germinal centers) cytotoxic (GZMB+CD8+ GZMB+CD68+ plus Th1 gene expression) immune responses. Analysis of versus inactive TLS untreated patients revealed former are associated with positive clinical outcomes. also contain regulatory (Tfr) which a CD25+CXCR5+GARP+FOXP3+ phenotype demethylated FOXP3 gene. Functional Tfr inhibited activities via glycoprotein repetitions predominant (GARP)-associated TGF-β–dependent mechanism. activity tumor-associated was dictated relative balance between TIL. These data mechanistic insight into processes orchestrated including activation immunological memory generation. regulated expected key target PD-1/PD-L1 blockade.

Language: Английский

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Biomarkers for breast cancer immunotherapy: PD-L1, TILs, and beyond

Expert Opinion on Investigational Drugs, Journal Year: 2021, Volume and Issue: 31(6), P. 549 - 555

Published: Nov. 18, 2021

Immune checkpoint inhibitors (ICIs) have recently entered into the therapeutic scenario of metastatic breast cancer. However, only a proportion patients benefit from ICIs and immune-based combinations, so identification reliable predictors response remains an unmet need.We discuss potential to in cancer, including PD-L1 expression, tumor-infiltrating lymphocytes (TILs), tumor mutational burden (TMB), several other biomarkers suggest future directions research this setting. A literature search was conducted October 2021 Pubmed/Medline, Cochrane library Scopus databases; addition, abstract international cancer meetings were reviewed.In terms immunotherapy TNBC patients, are being evaluated. Valuable data on predictive emerged, host-related factors, immune-related cells, protein genetic markers. Data supporting triple-negative setting not concordant, but there been some positive phase III trials IMpassion130 KEYNOTE-355. Phase II (neo)adjuvant supportive strategy. Further investigations warranted challenging area.

Language: Английский

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Immunotherapy for Hepatocellular Carcinoma: Current Status and Future Prospects

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: Oct. 4, 2021

Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer with poor prognosis. Surgery, chemotherapy, and radiofrequency ablation are three conventional therapeutic options that will help only a limited percentage of HCC patients. Cancer immunotherapy has achieved dramatic advances in recent years provides new opportunities to treat HCC. However, various etiologies can evade immune system through multiple mechanisms. With rapid development genetic engineering synthetic biology, variety novel immunotherapies have been employed advanced HCC, including checkpoint inhibitors, adoptive cell therapy, engineered cytokines, vaccines. In this review, we summarize current landscape research progress different strategies treatment The challenges field also discussed.

Language: Английский

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Role of the intestinal microbiome and microbial-derived metabolites in immune checkpoint blockade immunotherapy of cancer

Genome Medicine, Journal Year: 2021, Volume and Issue: 13(1)

Published: June 23, 2021

Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that block immune inhibitory pathways. Administration of ICIs augments T cell-mediated responses against tumor, resulting in improved overall survival cancer patients. It has emerged the intestinal microbiome can modulate to via host system and use antibiotics lead reduced efficacy ICIs. Recently, reports fecal microbiota transplantation ICI therapy patients previously refractory suggest targeting may be a viable strategy reprogram tumor microenvironment augment therapy. Intestinal microbial metabolites also linked response rates In addition rates, certain toxicities arise during have been found associated with microbiome, including particular colitis. A key mechanistic question is how microbes enhance anti-tumor or, alternatively, predispose ICI-associated Evidence outcomes therapies two major mechanisms, those antigen-specific antigen-independent. Antigen-specific mechanisms occur when epitopes shared between antigens could enhance, reduce cross-reactive adaptive cells. Antigen-independent include modulation by engaging innate and/or To establish microbiome-based biomarkers specifically immunotherapy, further prospective interventional studies will required.

Language: Английский

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