Russell W Jenkins, Associate Professor at Medical University of South Carolina, shared a post on LinkedIn about a recent article he and his colleagues co-authored, adding:
“It was an honor and a privilege to present at SITC 2025 in the Cellular Therapies for Solid Tumors, Cell Therapies beyond CAR T Cells Session! Thank you to the organizers, session chairs, and attendees!
So what did we discuss at SITC? Well, we have we learned a fair bit about how expanded tumor-infiltrating lymphocytes (TIL) kill cancer cells over the past few years. Quite unexpectedly, tumoricidal CD8+ TIL can eliminate tumor cells in a time- and dose-dependent but MHC-I-independent fashion. TIL-mediated cancer cell killing requires the coactivation of lymphotoxin beta receptor and inteferon sensing (JAK/STAT) pathways in cancer cells, and lymphotoxin beta (LTB)+ CD8+ T cells are enriched in expanded TIL. Additionally, enrichment of LTB+ CD8+ T cells in commercial TIL is associated with clinical response!
Lastly, LTB+ CD8+ TIL arise from a subset of putative neo-antigen reactive (NeoTCR8-high) tumor-infiltrating CD8+ T cells (that lack LTB expression). Together, these findings suggest that class I MHC expression is likely indispensable for generating tumor-reactive CD8+ T cells, but that these CD8+ T cells undergo ‘reprogramming’ during in vitro expansion, giving rise to a less exhausted, more tumoricidal CD8+ T cell population that is ‘licensed to kill’ cancer cells (even those lacking class I MHC machinery)! Many more questions to answer, but a series of very exciting findings.
Congrats to Hongyan Xie who has led this effort and to all our colleagues/collaborators at MGH and the Broad Institute. Additional thanks to our partners at Iovance Biotherapeutics. I’m also happy to share that the pre-print is now available online.”
Title: Lymphotoxin-driven cancer cell eradication by tumoricidal CD8+ TIL
Authors: Hongyan Xie, Aiping Jiang, Aonkon Dey, Joseph W. Dean, Jonathan J. Perera, Neal P. Smith, Alex C. Y. Chen, Seth Anderson, Angelina M. Cicerchia, Yi Sun, William A. Michaud, Maria Florentin, Jacy Fang, Or-Yam Revach, Tatyana Sharova, Aleigha Lawless, Katherine H. Xu, Yuhui Song, Bidish Patel, Jonathan D. Stevens, William J. Lane, Derin B. Keskin, Sonia Cohen, Donald P. Lawrence, Ryan J. Sullivan, Keith T. Flaherty, Genevieve M. Boland, Linda T. Nieman, Moshe Sade-Feldman, Nir Hacohen, Debattama R. Sen, Catherine Wu, Brian Gastman, Rongsu Qi, Hequn Yin, Alexandra-Chloé Villani, Robert T. Manguso, Russell W. Jenkins
Read the Full Article on bioRxiv
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