Posted: Thursday, November 14, 2024
Merkel cell polyomavirus–specific Merkel cell carcinoma tumor-infiltrating lymphocytes (TILs) seem to exhibit distinct transcriptional patterns compared with lung neoantigen TILs, according to Kellie N. Smith, PhD, of Sidney Kimmel Comprehensive Cancer Center, Baltimore, and colleagues. Their findings, which were presented during the 2024 Society for Immunotherapy of Cancer (SITC) Annual Meeting (Abstract 936), may have potential therapeutic implications.
The investigators used a technique coupling single-cell T-cell receptor and RNA sequencing with barcoded multimers against human leukocyte antigen–restricted Merkel cell polyomavirus epitopes on CD8-positive TILs from the treatment-naive metastatic lymph node lesions of three patients with Merkel cell carcinoma. Barcoded multimer reads and distribution patterns were analyzed, identifying 4,473 Merkel cell polyomavirus–specific TILs. Merkel cell carcinoma data were integrated with those of three anti–PD-1 antibody–treated primary lung cancers, in which 2,057 neoantigen-specific TILs were previously detected.
A dimension-reduction algorithm showed both lung neoantigen– and Merkel cell polyomavirus–specific TILs localized to tissue-resident memory regions, with 82% of the latter having been found in clusters with high CD103 and ZNF683 expression. Merkel cell polyomavirus–specific TILs appeared to exhibit high CXCL13 and ENTPD1 and low IL7R expression; this seemed to be consistent with published reports on neoantigen-specific TILs.
Despite sharing certain transcriptional features, Merkel cell polyomavirus– vs neoantigen-specific TILs were found to demonstrate differential expression of key genes implicating their functional state. Merkel cell polyomavirus–specific TILs expressed higher levels of CCR7, TCF7, GZMK, and LAG3—but not PDCD1. Of note, co-expression of GZMK and LAG3 was seen in more than half of the Merkel cell polyomavirus–specific TILs (53%). The investigators stated that “this transcriptional program has been associated with a highly proliferative stem-like pool capable of rapid antigen targeting upon immune checkpoint blockade.”
Disclosure: No information regarding conflicts of interest was provided.