Fingolimod and tumor-infiltrating lymphocytes in checkpoint-inhibitor treated cancer patients

Cancer Immunol Immunother. 2021 Feb;70(2):563-568. doi: 10.1007/s00262-020-02693-7. Epub 2020 Aug 17.

Abstract

Immune checkpoint inhibitors (ICIs) are emerging as the new standard of care for treating various metastatic cancers. It is known that effective anti-tumor immune responses are associated with a stronger presence of tumor-infiltrating lymphocytes (TILs) in solid tumor tissue. Cancer patients with relapsing-remitting multiple sclerosis (RRMS) are often under continuous treatment with fingolimod, an immune-modulating drug that inhibits lymphocyte egress from secondary lymphatic organs. Little is known about the effect of fingolimod on ICI cancer therapy, as fingolimod may limit the number of TILs. Here we present three patients with RRMS, who developed various cancers during fingolimod treatment. Histology of all tumors consistently showed low numbers of TILs. A second biopsy taken from one of the tumors, a melanoma, revealed a significant increase of TILs after stopping fingolimod and starting pembrolizumab, indicating a surge in the number and re-invigoration of T cells. Our study suggests that fingolimod limits the number of TILs in solid tumors and may, thus, inhibit anti-cancer immune responses.

Keywords: Cancer; Fingolimod; Immune checkpoint inhibitors; Multiple sclerosis; Oncology; Tumor immunology.

Publication types

  • Case Reports

MeSH terms

  • Female
  • Fingolimod Hydrochloride / pharmacology
  • Fingolimod Hydrochloride / therapeutic use*
  • Humans
  • Immune Checkpoint Inhibitors / pharmacology
  • Immune Checkpoint Inhibitors / therapeutic use*
  • Immunosuppressive Agents / pharmacology
  • Immunosuppressive Agents / therapeutic use*
  • Lymphocytes / immunology*
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Middle Aged
  • Neoplasms / drug therapy*
  • Neoplasms / immunology

Substances

  • Immune Checkpoint Inhibitors
  • Immunosuppressive Agents
  • Fingolimod Hydrochloride