Flash Talk & E-Poster Presentation 33rd Lorne Cancer Conference 2021

Tumour antigen-specific effector memory cytotoxic T lymphocytes (CTL) predict response to immune checkpoint blockade therapy (#48)

Nicola Principe 1 2 , Joel Kidman 1 2 , Caitlin M Tilsed 1 2 , Scott A Fisher 1 2 , Vanessa S Fear 3 , Catherine A Forbes 3 , Rachael M Zemek 3 , Abha Chopra 4 , Mark Watson 4 , Ian M Dick 1 2 , Louis Boon 5 , Robert A Holt 6 , Richard A Lake 1 2 , Anna K Nowak 2 7 , Willem J Lesterhuis 1 2 3 , Alison M McDonnell 1 2 3 , Jonathan Chee 1 2
  1. School of Biomedical Science, University of Western Australia, Crawley, WA, Australia
  2. National Centre for Asbestos Related Diseases, Institute for Respiratory Health, University of Western Australia, Nedlands, WA, Australia
  3. Telethon Kids Institute, Perth, WA, Australia
  4. Institute of Immunology and Infectious Diseases, Murdoch University, Murdoch, WA, Australia
  5. Polpharma Biologics, Utrecht, Netherlands
  6. BC Cancer Agency, Vancouver, British Columbia, Canada
  7. School of Medicine, University of Western Australia, Crawley, WA, Australia

Immune checkpoint therapy (ICPB) results in durable responses in individuals with some cancers, but not all patients respond to treatment. ICPB improves CD8+ cytotoxic T lymphocyte (CTL) function, but changes in tumor antigen-specific CTLs post-ICPB that correlate with successful responses have not been well characterized. Here, we studied murine tumor models with dichotomous responses to ICPB. We introduced a model tumor antigen (HA, hemagglutinin), tracked tumour (HA)-specific CTL frequencies and phenotype before and after ICPB in responding and non-responding animals. Tumor antigen-specific CTLs increased within tumor and draining lymph nodes after ICPB, and exhibited an effector memory-like phenotype, expressing IL-7R (CD127), KLRG1, T‑bet and granzyme B. Increased tumor antigen-specific CTLs corresponded to reduced TCR repertoire diversity within the tumor. Responding tumors exhibited higher infiltration of effector memory tumor antigen-specific CTLs, but lower frequencies of regulatory T cells compared to non-responders. Tumor antigen-specific CTLs persisted in responding animals and formed memory responses against tumor antigens. Our results suggest that increased effector memory tumor antigen-specific CTLs, in the presence of reduced immunosuppression within tumors is part of a successful ICPB response. Temporal and nuanced analysis of T cell subsets provides a potential new source of immune based biomarkers for response to ICPB.