Zhang CY, Liu S, Yang M. Nutrition deprivation affects the cytotoxic effect of CD8 T cells in hepatocellular carcinoma. World J Gastrointest Oncol 2022; 14(9): 1887-1891 [PMID: 36187392 DOI: 10.4251/wjgo.v14.i9.1887]
Corresponding Author of This Article
Ming Yang, DVM, PhD, Postdoctoral Fellow, Department of Surgery, University of Missouri, Room 2203, NexGen Precision Building, 1030 Hitt Street, Columbia, MI 65211, United States. yangmin@health.missouri.edu
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Letter to the Editor
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastrointest Oncol. Sep 15, 2022; 14(9): 1887-1891 Published online Sep 15, 2022. doi: 10.4251/wjgo.v14.i9.1887
Nutrition deprivation affects the cytotoxic effect of CD8 T cells in hepatocellular carcinoma
Chun-Ye Zhang, Shuai Liu, Ming Yang
Chun-Ye Zhang, Department of Veterinary Pathobiology, University of Missouri, Columbia, MO 65211, United States
Shuai Liu, The First Affiliated Hospital, Zhejiang University, Hangzhou 310006, Zhejiang Province, China
Ming Yang, Department of Surgery, University of Missouri, Columbia, MO 65211, United States
Author contributions: Zhang CY, Liu S, and Yang M designed, collected data, wrote, revised, and finalized the manuscript, contributed equally, and shared the first authorship.
Conflict-of-interest statement: All authors declare no conflicts of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Ming Yang, DVM, PhD, Postdoctoral Fellow, Department of Surgery, University of Missouri, Room 2203, NexGen Precision Building, 1030 Hitt Street, Columbia, MI 65211, United States. yangmin@health.missouri.edu
Received: June 18, 2022 Peer-review started: June 18, 2022 First decision: July 19, 2022 Revised: July 28, 2022 Accepted: August 16, 2022 Article in press: August 16, 2022 Published online: September 15, 2022
Abstract
Hepatocellular carcinoma (HCC) is the most common type of liver cancer and the third leading cause of cancer-related death worldwide. Factors including carcinogens, infection of hepatitis viruses, alcohol abuse, and metabolic disorders such as non-alcoholic fatty liver disease mainly contribute to HCC initiation and progression. Immunotherapy is one of the most powerful tools for unresectable HCC treatment in patients. CD8+ T cells are a major immune component in the tumor microenvironment with cytotoxic effects against cancer cells. However, these CD8+ T cells commonly display an exhaustion phenotype with high expression of programmed cell death protein 1, T-cell immunoglobulin and mucin-domain containing-3, and/or lymphocyte-activation gene 3, producing low levels of perforin (PRF1) and granzyme B (GZMB), as well as anti-tumor cytokines, such as interferon gamma and tumor necrosis factor alpha. In the referenced study, the authors also showed that deprivation of glutamine decreased the antitumor function of CD8+ T cells, as well as the production of PRF1 and GZMB. However, the role of each amino acid in T cell function and exhaustion may depend on tumor type and tumor microenvironment, including the source of other nutrients. Overall, amino acids or other nutrient metabolites in the tumor microenvironment play a pivotal role in both tumor growth and immune response.
Core Tip: Immunotherapy is one of the most powerful tools for patients with unresectable hepatocellular carcinoma. CD8+ T cells are a major immune component in the tumor microenvironment with cytotoxic effects against tumor cells. However, these CD8+ T cells commonly display an exhaustion phenotype with high expression of immune checkpoints such as programmed cell death protein 1, producing less anti-tumor proteins and cytokines, such as perforin and granzyme B. Here, we show that the roles of amino acids such as glutamine in T cell activation and function are dependent on tumor types and nutrients in the tumor microenvironment. Overall, nutrient metabolism reprogramming in the tumor microenvironment plays a pivotal role in both tumor growth and immune response.
