IRCCS Humanitas Research Hospital & Humanitas University

There is a newer version of the record available.

Published May 17, 2024 | Version v1
Dataset Open

Dataset #2 related to article "NaCl enhances CD8+ T-cell effector functions in cancer immunotherapy"

Authors/Creators

  • 1. ROR icon IRCCS Humanitas Research Hospital
  • 2. UoS Milan
  • 3. ROR icon Leibniz Institute for Immunotherapy
  • 4. ROR icon University of Cambridge
  • 5. ROR icon Humanitas University
  • 6. ROR icon University of Melbourne
  • 7. University of Piemonte

Description

CD8+ T cells control tumors but inevitably become dysfunctional. Ionic metabolism is emerging as a regulator of CD8+ T cells in anti-tumor immunity. We show that sodium chloride (NaCl) counteracts T-cell dysfunction to promote cancer regression. NaCl supplementation during CD8+ T-cell culture induced potent effector differentiation, IFN-g production and cytotoxicity while maintaining gene networks responsible for stem-like plasticity. Accordingly, adoptive transfer of tumor-specific T cells resulted in superior anti-tumor immunity in a humanized model. In mice, high-salt diet reduced growth of experimental tumors in a CD8+ T cell-dependent manner, by inhibiting terminal differentiation, and by enhancing the effector potency of CD8+ T cells. Mechanistically, NaCl enhanced glutamine consumption that was critical for transcriptional, epigenetic and functional reprogramming. In humans, CD8+ T cells undergoing antigen recognition in tumors and predicting favorable response to checkpoint blockade immunotherapy resembled those induced by NaCl. Thus, NaCl metabolism is a major regulator of CD8+ T-cell effector function, with potential translation in cancer immunotherapy.

Files

Dataset_4_raw_count_matrix.txt

Files (35.4 GB)

Name Size Download all
md5:5c2ff8aee41d24091b80478bd880140e
11.9 MB Preview Download
md5:14c21ccc96b7df451bd3d92ee593c141
2.9 GB Download
md5:cae5172f09003a3973024ba37bc0295c
2.8 GB Download
md5:dde014e8d769630f8e34d12c1c95352d
3.4 GB Download
md5:5d607c33ab2aca777b44dcf2c5f350e2
2.8 GB Download
md5:c726023075b67757acc91c5402a838ee
3.1 GB Download
md5:23d8f9fa267d37aadb1cfd4c83a25025
3.0 GB Download
md5:391cdaa8c2b164888c6741c6393ea9e4
2.8 GB Download
md5:2d6afd0297fef377d6c14a6a0630d91b
3.1 GB Download
md5:ad34522040f5424b6ba27646ee3a7c86
2.9 GB Download
md5:8844dee59aaa38c2986194646fc04636
3.3 GB Download
md5:e68cfbc31e5fbaefcaa87551abb5365e
2.5 GB Download
md5:069d77542ec382c789a83ebf50244612
2.8 GB Download
md5:eb8dde98b4e1f5a2c9a048479f15e656
20.7 kB Download