ER-Golgi Network Regulates Anti-Tumor T Cell Immunotherapeutic Response

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Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B167
Abstract ID: 6045

Presenting Author:
Nathaniel Oberholtzer , Student at Med. Univ. of South Carolina

Abstract:

The tumor microenvironment mediated disruption of Golgi architecture and function, termed Golgi stress, via altered redox signaling in the regulation of T cell survival and function are largely unknown. Here we show that the disruption of Golgi architecture, identified by the decreased expression if GM130, was reverted upon treatment with hydrogen sulfide (H₂S) donor GYY4137, or over-expressing cystathionine β-synthase (Cbs), an enzyme involved in the biosynthesis of endogenous H₂S – that promoted stemness, antioxidant capacity and exhibited increased protein translation mediated in part by Peroxiredoxin-4. In in vivo models of melanoma and lymphoma, anti-tumor T cells conditioned ex vivo with exogenous H₂S or overexpressing Cbs demonstrated superior tumor control upon adoptive transfer. Further, Golgi^hi T cell subset exhibited unique metabolic signature and enhanced anti-tumor capacity. These data suggest that intrinsic H₂S is an immunomodulatory agent that regulates the efficacy of ACT, by mitigating Golgi stress and preserving its structure and function that define T cell anti-tumor capacity.