PD-1 blockade induces reactivation of non-productive T cell responses characterized by NF-kB signaling in patients with pancreatic cancer.
Lestat R AliPatrick J LenehanVictoire Cardot-RuffinoAndressa Dias CostaMatthew H G KatzTodd W BauerJonathan Andrew NowakBrian M WolpinThomas A AbramsAnuj K PatelThomas E ClancyJiping WangJoseph D ManciasMatthew J ReilleyChee-Chee H StuckyTanios S Bekaii-SaabRawad EliasNipun B MerchantCraig L SlingluffOsama E RahmaStephanie K DouganPublished in: Clinical cancer research : an official journal of the American Association for Cancer Research (2023)
Cytotoxic T cells in the blood of PDAC patients remain sensitive to reinvigoration by PD-1 blockade and some have tumor-recognizing potential. Although these T cells proliferate and have a signature of IFN exposure, they also upregulate NF-κB signaling, which potentially counteracts the beneficial effects of anti-PD-1 reinvigoration and marks these T cells as non-productive contributors to anti-tumor immunity.