Chromosomes from mouse T cells exhibiting telomeres in inexperienced. Credit score: Immunity (2025). DOI: 10.1016/j.immuni.2025.08.008
Tumors are anxious locations for cancer-fighting immune cells. Low oxygen, excessive acid ranges, and different stressors put pressure on mitochondria, the cell’s power factories, resulting in T cell exhaustion and poor most cancers outcomes.
New analysis revealed in Immunity by researchers on the College of Pittsburgh discovered that in mice, the poisonous tumor setting causes mitochondria to generate reactive oxygen species (ROS) that journey to the nucleus and harm telomeres, driving T cells to a dysfunctional state.
“The really exciting part about this research is that by preventing damage to telomeres via a targeted antioxidant, we can rescue T cell function,” mentioned lead creator Dayana Rivadeneira, assistant professor within the Pitt Division of Immunology and UPMC Hillman Most cancers Middle. “This opens the door to novel therapies to improve the effectiveness of cancer immunotherapies.”
Rivadeneira and senior creator Greg Delgoffe, professor within the Pitt Division of Immunology and UPMC Hillman, did not got down to research telomeres. That they had initially been how harm to mitochondria can have an effect on T cell perform. However a collaboration with Patricia Opresko, professor within the Pitt Division of Pharmacology and Chemical Biology, and the late Marcel Bruchez, professor of organic sciences and chemistry at Carnegie Mellon College, led them to contemplate telomeric harm, too.
The researchers created mice endowed with a genetic system that—when uncovered to far-red mild—generates extremely focused oxidative harm both at telomeres or mitochondria.
“What we found was remarkable,” mentioned Delgoffe. “Whether we damaged the mitochondria or the telomeres, we got the same result: dysfunctional T cells. There is crosstalk between the engine of the cell and the brains of the cell, the mitochondria and the nucleus. This is something we didn’t necessarily appreciate, at least in the immune system.”
“When you damage the mitochondria, one of the first things that gets damaged is the telomeres,” Rivadeneira added. “And, likewise, when you damage the telomeres, they talk back to the mitochondria to initiate a program that tells the cell to shut down and become exhausted.”
As a result of ROS—extremely reactive oxygen molecules that trigger mobile harm—have been answerable for telomeric harm, Delgoffe and Rivadeneira hypothesized that ROS-neutralizing antioxidants may shield or restore T cell perform.
To neutralize ROS particularly at telomeres, they took mouse T cells and tethered an antioxidant protein to a different protein that resides at telomeres. After they infused these T cells into mice with an aggressive type of melanoma, the animals had a lot better survival and smaller tumors than these given common T cells.
In line with the researchers, this antioxidant method might be utilized to CAR-T remedy, which entails taking a affected person’s T cells and genetically engineering them to raised acknowledge most cancers cells earlier than reinfusing them.
“This research is highly translatable because this approach could easily be incorporated into standard CAR-T protocol,” mentioned Delgoffe. “While you’re genetically engineering T cells to improve cancer-fighting capability, you could also make them bulletproof against oxidative damage.”
Now, the researchers are working to develop the same telomere-specific antioxidant method for modifying human T cells, which they finally hope to check in scientific trials.
In her newly launched lab, Rivadeneira additionally plans to analyze extra broadly how telomere well being influences the immune system and most cancers outcomes. One space of curiosity is knowing how chemotherapy alters T cell perform by damaging telomeres and whether or not this might affect whether or not sufferers reply to immunotherapy.
Extra data:
Dayana B. Rivadeneira et al, Oxidative-stress-induced telomere instability drives T cell dysfunction in most cancers, Immunity (2025). DOI: 10.1016/j.immuni.2025.08.008
Offered by
College of Pittsburgh
Quotation:
Antioxidant protect for T cell telomeres exhibits promise in opposition to tumor-induced exhaustion (2025, September 10)
retrieved 11 September 2025
from https://medicalxpress.com/information/2025-09-antioxidant-shield-cell-telomeres-tumor.html
This doc is topic to copyright. Other than any honest dealing for the aim of personal research or analysis, no
half could also be reproduced with out the written permission. The content material is supplied for data functions solely.
