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

Ali Hasan, Fiamma Berner, Christoph Jakob Ackermann, Sandra Ring, Alexandre Moulin, Joachim Müller, Eva Markert, Oltin Pop, Stefanie Müller, Stefan Diem, Thomas Hundsberger & Lukas Flatz

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.
   
citation Hasan A, Berner F, Ackermann C J, Ring S, Moulin A, Müller J, Markert E, Pop O, Müller S, Diem S, Hundsberger T, Flatz L. Fingolimod and tumor-infiltrating lymphocytes in checkpoint-inhibitor treated cancer patients. Cancer Immunol Immunother 2020; 70:563-568.
   
type journal paper/review (English)
date of publishing 17-08-2020
journal title Cancer Immunol Immunother (70/2)
ISSN electronic 1432-0851
pages 563-568
PubMed 32804246
DOI 10.1007/s00262-020-02693-7