4.6 Article

Immune signature as predictive marker for response to checkpoint inhibitor immunotherapy and overall survival in melanoma

Journal

CANCER MEDICINE
Volume 10, Issue 5, Pages 1562-1575

Publisher

WILEY
DOI: 10.1002/cam4.3710

Keywords

checkpoint inhibitor; immunotherapy; malignant melanoma; myeloid-derived suppressor cells; platelets

Categories

Funding

  1. German Cancer Consortium (DKTK)
  2. German Research Foundation [CRC 1066-B3]
  3. Wilhelm Sander Foundation
  4. Fulbright US Student Grant
  5. Prof. Rochelmeyer Foundation of the Johannes Gutenberg-University Mainz

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This study found a distinct immune signature in the peripheral blood of melanoma patients before treatment that could predict response to immune checkpoint inhibitor therapy. Responders to therapy exhibited specific immune cell compositions, but even non-responders with similar compositions still benefited from treatment.
Background Malignant melanoma is an immunogenic skin cancer with an increasing global incidence. Advanced stages of melanoma have poor prognoses. Currently, there are no reliable parameters to predict a patient's response to immune checkpoint inhibitor (ICI) therapy. Methods This study highlights the relevance of a distinct immune signature in the blood for response to ICI therapy and overall survival (OS). Therefore, the immune cell composition in the peripheral blood of 45 melanoma patients prior to ICI therapy was analyzed by flow cytometry and complete blood count. Results Responders to ICI therapy displayed an abundance of proliferating CD4(+) T cells, an increased lymphocyte-to-monocyte ratio, a low platelet-to-lymphocyte ratio, low levels of CTLA-4(+) Treg, and (arginase 1(+)) polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC). Nevertheless, non-responders with similar immune cell compositions also benefited from therapy displaying increased long-term OS. Conclusions Our study demonstrated that the observed immune signature in the peripheral blood of melanoma patients prior to treatment could identify responders as well as non-responders that benefit from ICI immunotherapies.

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