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

Cancer Med. 2021 Mar;10(5):1562-1575. doi: 10.1002/cam4.3710. Epub 2021 Jan 15.

Abstract

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.

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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / immunology
  • Blood Cell Count
  • CD4-Positive T-Lymphocytes / cytology
  • Female
  • Flow Cytometry
  • Humans
  • Immune Checkpoint Inhibitors / therapeutic use*
  • Immunity, Cellular
  • Immunotherapy, Adoptive*
  • Lymphocyte Count
  • Male
  • Melanoma / blood
  • Melanoma / immunology*
  • Melanoma / mortality
  • Melanoma / therapy*
  • Melanoma, Cutaneous Malignant
  • Middle Aged
  • Monocytes / cytology
  • Myeloid-Derived Suppressor Cells / cytology
  • Platelet Count
  • Receptors, Chimeric Antigen
  • Skin Neoplasms / blood
  • Skin Neoplasms / immunology*
  • Skin Neoplasms / mortality
  • Skin Neoplasms / therapy*
  • Survival Analysis
  • T-Lymphocytes, Regulatory / cytology

Substances

  • Biomarkers, Tumor
  • Immune Checkpoint Inhibitors
  • Receptors, Chimeric Antigen