PolarTIL programming reveals an essential role for TGF-β1 in antitumor memory in human cutaneous malignancies
Abstract
Tumor-infiltrating lymphocyte (TIL) therapy can induce tumor regression in solid malignancies, yet durable responses remain limited, highlighting the need for more effective cell products. Here, we generated a novel TIL product, PolarTIL, by polarizing murine and human TIL from cutaneous malignancies ex vivo with a defined Type-17 cytokine cocktail. Compared with conventional IL-2 culture, PolarTIL produced greater cell yields and a distinct cellular state marked by reduced CD4⁺ regulatory T cells, enrichment of CD103⁺ populations, and superior antitumor activity in vitro and in vivo . Unexpectedly, TGF-β1 emerged as a critical regulator of PolarTIL function. Although TGF-β is commonly targeted for inhibition in cancer immunotherapy, its removal during PolarTIL generation completely abolished therapeutic efficacy in vivo . Together, these findings reveal an unrecognized requirement for TGF-β1 in programming effective TIL responses and establish PolarTIL as a promising next-generation cellular therapy for solid tumors.
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BibTeX
@misc{wyatt2026polartil,
title = {{PolarTIL programming reveals an essential role for TGF-β1 in antitumor memory in human cutaneous malignancies}},
author = {Megan Wyatt and Rachel Mason and James Carmouche and Ayana Ruffin and Megen Wittling and Anna Cole and Aubrey Smith and Guillermo Rangel Rivera and Michael Ware and Michael Lowe and Keith Delman and Nathaniel Wilson and Gregory B. Lesinski and Chrystal Paulos},
howpublished = {Research Square},
year = {2026},
month = oct,
doi = {10.21203/rs.3.rs-11309475/v1},
url = {https://doi.org/10.21203/rs.3.rs-11309475/v1},
note = {CC BY 4.0},
}
RIS
TY - UNPB
TI - PolarTIL programming reveals an essential role for TGF-β1 in antitumor memory in human cutaneous malignancies
AU - Megan Wyatt
AU - Rachel Mason
AU - James Carmouche
AU - Ayana Ruffin
AU - Megen Wittling
AU - Anna Cole
AU - Aubrey Smith
AU - Guillermo Rangel Rivera
AU - Michael Ware
AU - Michael Lowe
AU - Keith Delman
AU - Nathaniel Wilson
AU - Gregory B. Lesinski
AU - Chrystal Paulos
PY - 2026
DA - 2026/10/30
PB - Research Square
DO - 10.21203/rs.3.rs-11309475/v1
UR - https://doi.org/10.21203/rs.3.rs-11309475/v1
AB - Tumor-infiltrating lymphocyte (TIL) therapy can induce tumor regression in solid malignancies, yet durable responses remain limited, highlighting the need for more effective cell products. Here, we generated a novel TIL product, PolarTIL, by polarizing murine and human TIL from cutaneous malignancies ex vivo with a defined Type-17 cytokine cocktail. Compared with conventional IL-2 culture, PolarTIL produced greater cell yields and a distinct cellular state marked by reduced CD4⁺ regulatory T cells, enrichment of CD103⁺ populations, and superior antitumor activity in vitro and in vivo . Unexpectedly, TGF-β1 emerged as a critical regulator of PolarTIL function. Although TGF-β is commonly targeted for inhibition in cancer immunotherapy, its removal during PolarTIL generation completely abolished therapeutic efficacy in vivo . Together, these findings reveal an unrecognized requirement for TGF-β1 in programming effective TIL responses and establish PolarTIL as a promising next-generation cellular therapy for solid tumors.
SN - 2693-5015
ER -