With @franklowery our new study on attributes of T cells that contribute to successful cell therapy in cancer patients in @ScienceMagazine today w/ colleagues @slgoff_SB, @NCI_CCR_SB @theNCI a TL;DR thread on key findings with caveats :) 1/10

has a long history of using tumor infiltrating T cells (TILs) to treat cancers since well.. before I was even born. We analyzed our most successful melanoma ACT trial for cell surface phenotypes in TIL infusion products of patients (aPD1/immunotherapy naive) /2

Surprisingly we found a CD39- TIL subset (CD39-CD69-, DN) associated with ACT-response. TBH we were expecting the opposite (CD39+). We only included CD39 bcz multiple groups (e.g. Simoni et al, 2018) had reported CD39+ as enriching for anti-tumor/neoantigen reactive T cells. /3

CD39- DN TILs RNA/epigenetics resemble stem-like memory progenitors, and in vitro were able to self-renew, and give rise to other CD39+ subsets. OTOH the most dominant subset of patient infusion products were CD39+ CD69+ (DP) and these guys were terminally differentiated.. /4

So, to clarify we specifically analyzed tumor-specific mutation-reactive Tcells. Turns out, ACT-responders had pool of neoantigen-reactive TILs in the CD39- phenotype, while non-responders did not (despite other irrelevant CD39- Tcells) -> not all CD39- T cells are bystanders /5