Targeting MDSC for Immune-Checkpoint Blockade in Cancer Immunotherapy: Current Progress and New Prospects

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Abstract

Immune-checkpoint blockade (ICB) demonstrated inspiring effect and great promise in anti-cancer therapy. However, many obstacles, such as drug resistance and difficulty in patient selection, limited the efficacy of ICB therapy and awaited to be overcome. By timely identification and intervention of the key immune-suppressive promotors in the tumor microenvironment (TME), we may better understand the mechanisms of cancer immune-escape and use novel strategies to enhance the therapeutic effect of ICB. Myeloid-derived suppressor cell (MDSC) is recognized as a major immune suppressor in the TME. In this review, we summarized the roles MDSC played in the cancer context, focusing on its negative biologic functions in ICB therapy, discussed the strategies targeted on MDSC to optimize the diagnosis and therapy process of ICB and improve the efficacy of ICB therapy against malignancies.

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Pembrolizumab versus Chemotherapy for PD-L1–Positive Non–Small-Cell Lung Cancer

Martin Reck, Delvys Rodriguez-Abreu, Andrew G Robinson … (2016)

Pembrolizumab is a humanized monoclonal antibody against programmed death 1 (PD-1) that has antitumor activity in advanced non-small-cell lung cancer (NSCLC), with increased activity in tumors that express programmed death ligand 1 (PD-L1).

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Signatures of T cell dysfunction and exclusion predict cancer immunotherapy response

X Liu, Shengqing Gu, Deng Pan … (2018)

Cancer treatment by immune checkpoint blockade (ICB) can bring long-lasting clinical benefits, but only a fraction of patients respond to treatment. To predict ICB response, we developed TIDE, a computational method to model two primary mechanisms of tumor immune evasion: the induction of T cell dysfunction in tumors with high infiltration of cytotoxic T lymphocytes (CTL) and the prevention of T cell infiltration in tumors with low CTL level. We identified signatures of T cell dysfunction from large tumor cohorts by testing how the expression of each gene in tumors interacts with the CTL infiltration level to influence patient survival. We also modeled factors that exclude T cell infiltration into tumors using expression signatures from immunosuppressive cells. Using this framework and pre-treatment RNA-Seq or NanoString tumor expression profiles, TIDE predicted the outcome of melanoma patients treated with first-line anti-PD1 or anti-CTLA4 more accurately than other biomarkers such as PD-L1 level and mutation load. TIDE also revealed new candidate ICB resistance regulators, such as SERPINB9 , demonstrating utility for immunotherapy research.

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Improved Survival with Ipilimumab in Patients with Metastatic Melanoma

F. Stephen Hodi, Steven J O'Day, David F McDermott … (2010)

An improvement in overall survival among patients with metastatic melanoma has been an elusive goal. In this phase 3 study, ipilimumab--which blocks cytotoxic T-lymphocyte-associated antigen 4 to potentiate an antitumor T-cell response--administered with or without a glycoprotein 100 (gp100) peptide vaccine was compared with gp100 alone in patients with previously treated metastatic melanoma. A total of 676 HLA-A*0201-positive patients with unresectable stage III or IV melanoma, whose disease had progressed while they were receiving therapy for metastatic disease, were randomly assigned, in a 3:1:1 ratio, to receive ipilimumab plus gp100 (403 patients), ipilimumab alone (137), or gp100 alone (136). Ipilimumab, at a dose of 3 mg per kilogram of body weight, was administered with or without gp100 every 3 weeks for up to four treatments (induction). Eligible patients could receive reinduction therapy. The primary end point was overall survival. The median overall survival was 10.0 months among patients receiving ipilimumab plus gp100, as compared with 6.4 months among patients receiving gp100 alone (hazard ratio for death, 0.68; P<0.001). The median overall survival with ipilimumab alone was 10.1 months (hazard ratio for death in the comparison with gp100 alone, 0.66; P=0.003). No difference in overall survival was detected between the ipilimumab groups (hazard ratio with ipilimumab plus gp100, 1.04; P=0.76). Grade 3 or 4 immune-related adverse events occurred in 10 to 15% of patients treated with ipilimumab and in 3% treated with gp100 alone. There were 14 deaths related to the study drugs (2.1%), and 7 were associated with immune-related adverse events. Ipilimumab, with or without a gp100 peptide vaccine, as compared with gp100 alone, improved overall survival in patients with previously treated metastatic melanoma. Adverse events can be severe, long-lasting, or both, but most are reversible with appropriate treatment. (Funded by Medarex and Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00094653.)

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Author and article information

Journal

Journal ID (nlm-ta): Clin Med Insights Oncol

Journal ID (iso-abbrev): Clin Med Insights Oncol

Journal ID (publisher-id): ONC

Journal ID (hwp): sponc

Title: Clinical Medicine Insights. Oncology

Publisher: SAGE Publications (Sage UK: London, England )

ISSN (Electronic): 1179-5549

Publication date (Electronic): 5 August 2021

Publication date Collection: 2021

Volume: 15

Electronic Location Identifier: 11795549211035540

Affiliations

[1-11795549211035540]Department of Urology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Institute of Urology, Nanjing University, Nanjing, 210008, People’s Republic of China

Author notes

[*]Hongqian Guo, Department of Urology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Institute of Urology, Nanjing University, Zhongshan Road 321#, Gulou District, Nanjing, China. Email: doctorghq@ 123456gmail.com

[*]Rong Yang, Department of Urology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Institute of Urology, Nanjing University, Zhongshan Road 321#, Gulou District, Nanjing, China. Email: doctoryr@ 123456gmail.com

Author information

Rong Yang https://orcid.org/0000-0001-8741-7121

Article

Publisher ID: 10.1177_11795549211035540 Publisher-manuscript ID: ONC-20-0120.R1

DOI: 10.1177/11795549211035540

PMC ID: 8365012

PubMed ID: 34408525

SO-VID: ef9f6676-da9e-4723-8dc2-2c763b2b8809

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This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

History

Date received : 5 November 2020

Date accepted : 7 July 2021

Funding

Funded by: National Natural Science Foundation of China, ;

Award ID: 81772710

Funded by: National Natural Science Foundation of China, ;

Award ID: 81772727

Funded by: Nanjing Science and technology Development Key Project, ;

Award ID: YKK19011

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cover-date January-December 2021

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ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: myeloid-derived suppressor cells,icb,pd-(l) 1,tme,immune escape

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ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: myeloid-derived suppressor cells, icb, pd-(l) 1, tme, immune escape

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Targeting MDSC for Immune-Checkpoint Blockade in Cancer Immunotherapy: Current Progress and New Prospects

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Cancer Immunotherapy

Most cited references 187

Pembrolizumab versus Chemotherapy for PD-L1–Positive Non–Small-Cell Lung Cancer

Signatures of T cell dysfunction and exclusion predict cancer immunotherapy response

Improved Survival with Ipilimumab in Patients with Metastatic Melanoma

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Cited by 37

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