A combination of PD‑1/PD‑L1 inhibitors: The prospect of overcoming the weakness of tumor immunotherapy (Review)

Kong, Xianbin; Lü, Peng; Liu, Chuanxin; Guo, Yuzhu; Yang, Yuying; Pan, Yingying; Wang, Fangyuan; Bo, Zhichao; Dou, Xiaoxin; Shi, Haoyang; Jing-yan, Meng

doi:10.3892/mmr.2021.12001

Cited by 21 publications

(11 citation statements)

References 159 publications

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“…Although the VSIR antagonist’s monotherapy did not show any effect based on preclinical studies, the combination of VSIR and CTLA-4 or PD-1 significantly reduced the number of tumor-recruiting T cells, thereby inducing antitumor responses against squamous cell carcinoma ( Kondo et al, 2016 ). In addition, studies have found that patients who show resistance to PD-1/CTLA-4-targeting therapies may benefit from VSIR blockade ( Kong et al, 2021 ). Moreover, CA-170, an orally administered dual inhibitor of VISTA and PD-L1, has shown clinical efficacy in phase I and II clinical trials in several advanced solid tumor types ( Sasikumar et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Identify the Prognostic and Immune Profile of VSIR in the Tumor Microenvironment: A Pan-Cancer Analysis

Liu

Zhang

Wang

et al. 2022

Front. Cell Dev. Biol.

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VSIR is a critical immunomodulatory receptor that inhibits T cell effector function and maintains peripheral tolerance. However, the mechanism by which VSIR participates in tumor immunity in the pan-cancer tumor microenvironment remains unclear. This study systematically explored the prognostic and immune profile of VSIR in the tumor microenvironment of 33 cancers. We compared the expression patterns and molecular features of VSIR in the normal and cancer samples both from the public databases and tumor chips. VSIR level was significantly related to patients’ prognosis and could be a promising predictor in many tumor types, such as GBM, KIRC, SKCM, READ, and PRAD. Elevated VSIR was closely correlated with infiltrated inflammatory cells, neoantigens expression, MSI, TMB, and classical immune checkpoints in the tumor microenvironment. Enrichment signaling pathways analysis indicated VSIR was involved in several immune-related pathways such as activation, proliferation, and migration of fibroblast, T cell, mast cell, macrophages, and foam cell. In addition, VSIR was found to widely express on cancer cells, fibroblasts, macrophages, and T cells in many tumor types based on the single-cell sequencing analysis and co-express with M2 macrophage markers CD68, CD163 based on the immunofluorescence staining. Finally, we predicted the sensitive drugs targeting VSIR and the immunotherapeutic value of VSIR. In sum, VSIR levels strongly correlated with the clinical outcome and tumor immunity in multiple cancer types. Therefore, therapeutic strategies targeting VSIR in the tumor microenvironment may be valuable tools for cancer immunotherapy.

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Section: Discussionmentioning

confidence: 99%

Identify the Prognostic and Immune Profile of VSIR in the Tumor Microenvironment: A Pan-Cancer Analysis

Liu

Zhang

Wang

et al. 2022

Front. Cell Dev. Biol.

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“…Such chemotherapy-immunotherapy combinations have been carried out in clinical trials that have targeted patients with lung cancer and melanoma. As a result, an increase in treatment response was identified in pembrolizumab, with a difference of 26% compared to chemotherapy administered as the only method of treatment [42,43].…”

Section: Pd-l1mentioning

confidence: 99%

VISTA, PDL-L1, and BRAF—A Review of New and Old Markers in the Prognosis of Melanoma

et al. 2022

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Melanoma is currently known as one of the most aggressive malignant tumors. The prognostic factors and particularities of this neoplasm are a persistent hot topic in the medical field. This review has multiple purposes. First, we aim to summarize the known data regarding the histological and immunohistochemical appearance of this versatile tumor and to look further into the analysis of several widely used prognostic markers, such as B-Raf proto-oncogene, serine/threonine kinase BRAF. The second purpose is to analyze the data on the new prognostic markers, V-domain Immunoglobulin Suppressor of T cell Activation (VISTA) and Programmed death-ligand 1 (PD-L1). VISTA is a novel target that is considered to be highly important in determining the invasive potential and treatment response of a melanoma, and there are currently only a limited number of studies describing its role. PD-L1 is a marker with whose importance has been revealed in multiple types of malignancies, but its exact role regarding melanoma remains under investigation. In conclusion, the gathered data highlights the importance of correlations between these markers toward providing patients with a better outcome.

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“…However, therapy with these antibodies may be hampered by the polarization of macrophages within the tumor microenvironment (TME) into M2 tumor-associated macrophages (TAMs), which suppress antitumor immune responses and promote tumor growth by releasing anti-inflammatory cytokines and angiogenic factors [276]. Thus, Choo YW, et al, investigated whether repolarization of these macrophages can enhance the anticancer efficacy of aPD-L1.…”

Section: Potential Role Of Exosomes In Cancer Treatmentmentioning

confidence: 99%

Exosomes: Potential Disease Biomarkers and New Therapeutic Targets

et al. 2021

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Exosomes are extracellular vesicles released by cells, both constitutively and after cell activation, and are present in different types of biological fluid. Exosomes are involved in the pathogenesis of diseases, such as cancer, neurodegenerative diseases, pregnancy disorders and cardiovascular diseases, and have emerged as potential non-invasive biomarkers for the detection, prognosis and therapeutics of a myriad of diseases. In this review, we describe recent advances related to the regulatory mechanisms of exosome biogenesis, release and molecular composition, as well as their role in health and disease, and their potential use as disease biomarkers and therapeutic targets. In addition, the advantages and disadvantages of their main isolation methods, characterization and cargo analysis, as well as the experimental methods used for exosome-mediated drug delivery, are discussed. Finally, we present potential perspectives for the use of exosomes in future clinical practice.

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A combination of PD‑1/PD‑L1 inhibitors: The prospect of overcoming the weakness of tumor immunotherapy (Review)

Cited by 21 publications

References 159 publications

Identify the Prognostic and Immune Profile of VSIR in the Tumor Microenvironment: A Pan-Cancer Analysis

Identify the Prognostic and Immune Profile of VSIR in the Tumor Microenvironment: A Pan-Cancer Analysis

VISTA, PDL-L1, and BRAF—A Review of New and Old Markers in the Prognosis of Melanoma

Exosomes: Potential Disease Biomarkers and New Therapeutic Targets

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