Exposure to anti-PD-1 causes functional differences in tumor-infiltrating lymphocytes in rare solid tumors

Caitlin A. Creasy, Marie Andrée Forget, Gopal Singh, Coya Tapia, Mingxuan Xu, Bettzy Stephen, Sharjeel Sabir, Funda Meric-Bernstam, Cara Haymaker, Chantale Bernatchez, Aung Naing

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

The pervasive use of therapeutic antibodies targeting programmed cell death protein 1 (PD-1) to boost anti-tumor immunity has positioned this approach to become the standard-of-care for some solid tumor malignancies. However, little is known as to how blockade of PD-1 may alter the function or phenotype of tumor-infiltrating lymphocytes (TIL). We used our ongoing Phase II clinical trial of pembrolizumab for patients with rare solid tumors from various types (NCT02721732) with matched core biopsies taken at baseline and after initial dose of anti-PD-1 (15–21 days post-dose) to elucidate this question. One fresh core needle biopsy was used to propagate TIL ex vivo to analyze phenotype and function using flow cytometry in both CD8+ and CD4+ TIL populations. An enriched CTLA-4 expression in the CD4+ TIL population was observed in TIL expanded from the on-treatment samples compared to TIL expanded from the matched baseline (n = 22, p = 0.0007) but was not observed in patients who experienced tumor regression. Impact on functionality was evaluated by measuring secretion of 65 soluble factors by expanded TIL from 26 patients at baseline and on-treatment. The CD8+ TIL population demonstrated a diminished cytokine secretion profile post-pembrolizumab. Overall, our study assesses the ramifications of one dose of anti-PD-1 on TIL in rare solid tumor types.

Original languageEnglish (US)
Pages (from-to)2245-2251
Number of pages7
JournalEuropean Journal of Immunology
Volume49
Issue number12
DOIs
StatePublished - Dec 1 2019

Keywords

  • Anti-PD-1
  • CTLA-4
  • Immunotherapy
  • Rare solid tumors
  • TIL

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

MD Anderson CCSG core facilities

  • Clinical and Translational Research Center
  • ORION
  • Clinical Trials Office

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