{"id":66262,"date":"2025-09-15T21:48:11","date_gmt":"2025-09-15T21:48:11","guid":{"rendered":"https:\/\/www.europesays.com\/ie\/66262\/"},"modified":"2025-09-15T21:48:11","modified_gmt":"2025-09-15T21:48:11","slug":"scientists-find-a-way-to-bulletproof-t-cells-against-cancer","status":"publish","type":"post","link":"https:\/\/www.europesays.com\/ie\/66262\/","title":{"rendered":"Scientists Find a Way to \u201cBulletproof\u201d T Cells Against Cancer"},"content":{"rendered":"

\t\t\"T<\/a>Researchers at the University of Pittsburgh have discovered that the harsh environment inside tumors, characterized by low oxygen and high acidity, induces stress in T cells\u2019 mitochondria, which then release reactive oxygen species (ROS) that damage telomeres and drive T cell exhaustion. Credit: Shutterstock<\/p>\n

Telomere damage drives T cell exhaustion. Antioxidants restored their cancer-fighting strength in mice.<\/strong><\/p>\n

Tumor environments place heavy stress on immune cells that fight cancer. Limited oxygen, elevated acidity, and other harsh conditions overload mitochondria, the cell\u2019s energy producers, which contributes to T cell fatigue and worsens cancer outcomes.<\/p>\n

A new study in Immunity, led by researchers at the University of Pittsburgh<\/a>, showed in mice that these conditions prompt mitochondria to release reactive oxygen species (ROS). These molecules travel to the nucleus and damage telomeres, ultimately pushing T cells into a dysfunctional state.<\/p>\n

\u201cThe really exciting part about this research is that by preventing damage to telomeres via a targeted antioxidant, we can rescue T cell function,\u201d said lead author Dayana Rivadeneira, assistant professor in the Pitt Department of Immunology and UPMC Hillman Cancer Center. \u201cThis opens the door to novel therapies to improve the effectiveness of cancer immunotherapies.\u201d<\/p>\n

\"Chromosomes<\/a>Chromosomes from mouse T cells showing telomeres in green. Credit: Rivadeneira et al. (2025) Immunity
\nUnexpected mitochondrial connection<\/p>\n

Rivadeneira and senior author Greg Delgoffe, a professor in the Pitt Department of Immunology and UPMC Hillman, did not originally plan to investigate telomeres. Their initial focus was on how mitochondrial damage influences T cell performance. A collaboration with Patricia Opresko, professor in the Pitt Department of Pharmacology and Chemical Biology, and the late Marcel Bruchez, professor of biological sciences and chemistry at Carnegie Mellon University, expanded the study to include telomeric damage.<\/p>\n

\"Dayana<\/a>Dayana Rivadeneira, assistant professor in the University of Pittsburgh Department of Immunology and UPMC Hillman Cancer Center. Credit: University of Pittsburgh<\/p>\n

To explore this, the team engineered mice with a genetic system that produces highly localized oxidative damage at either telomeres or mitochondria when exposed to far-red light.<\/p>\n

\u201cWhat we found was remarkable,\u201d said Delgoffe. \u201cWhether 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\u2019t necessarily appreciate, at least in the immune system.\u201d<\/p>\n

\u201cWhen you damage the mitochondria, one of the first thing that gets damaged is the telomeres,\u201d Rivadeneira added. \u201cAnd, 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.\u201d<\/p>\n

Antioxidant therapy to restore function<\/p>\n

Because ROS \u2014 highly reactive oxygen molecules that cause cellular damage \u2014 were responsible for telomeric damage, Delgoffe and Rivadeneira hypothesized that ROS-neutralizing antioxidants could protect or restore T cell function.<\/p>\n

To neutralize ROS specifically at telomeres, they took mouse T cells and tethered an antioxidant protein to another protein that resides at telomeres. When they infused these T cells into mice with an aggressive form of melanoma, the animals had much better survival and smaller tumors than those given regular T cells.<\/p>\n

Potential for CAR-T therapy<\/p>\n

According to the researchers, this antioxidant approach could be applied to CAR-T therapy, which involves taking a patient\u2019s T cells and genetically engineering them to better recognize cancer cells before reinfusing them.<\/p>\n

\u201cThis research is highly translatable because this approach could easily be incorporated into standard CAR-T protocol,\u201d said Delgoffe. \u201cWhile you\u2019re genetically engineering T cells to improve cancer-fighting capability, you could also make them bulletproof against oxidative damage.\u201d<\/p>\n

\"Fluorescent<\/a>Left photo \u2014 Chromosomes from mouse T cells showing telomeres in green. Credit: Rivadeneira et al. (2025) Immunity. Right Photo, Dayana Rivadeneira (left) and Greg Delgoffe. Credit: University of Pittsburgh<\/p>\n

Now, the researchers are working to develop a similar telomere-specific antioxidant approach for modifying human T cells, which they eventually hope to test in clinical trials.<\/p>\n

In her newly launched lab, Rivadeneira also plans to investigate more broadly how telomere health influences the immune system and cancer outcomes. One area of interest is understanding how chemotherapy alters T cell function by damaging telomeres and whether this could influence whether patients respond to immunotherapy.<\/p>\n

Reference: \u201cOxidative-stress-induced telomere instability drives T cell dysfunction in cancer\u201d by Dayana B. Rivadeneira, Sanjana Thosar, Kevin Quann, William G. Gunn, Victoria G. Dean, Bingxian Xie, Angelina Parise, Andrew C. McGovern, Kellie Spahr, Konstantinos Lontos, Ryan P. Barnes, Marcel P. Bruchez, Patricia L. Opresko and Greg M. Delgoffe, 9 September 2025, Immunity.
DOI: 10.1016\/j.immuni.2025.08.008<\/a><\/p>\n

Funding: NIH\/National Institutes of Health, Cancer Research Institute, Mark Foundation For Cancer Research<\/p>\n

Never miss a breakthrough: Join the SciTechDaily newsletter.<\/a><\/b><\/p>\n","protected":false},"excerpt":{"rendered":"Researchers at the University of Pittsburgh have discovered that the harsh environment inside tumors, characterized by low oxygen…\n","protected":false},"author":2,"featured_media":66263,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[78],"tags":[110,18,135,19,5533,4701,17,7818,1668,46466],"class_list":{"0":"post-66262","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-health","8":"tag-cancer","9":"tag-eire","10":"tag-health","11":"tag-ie","12":"tag-immunology","13":"tag-immunotherapy","14":"tag-ireland","15":"tag-mitochondria","16":"tag-t-cells","17":"tag-university-of-pittsburgh"},"share_on_mastodon":{"url":"","error":""},"_links":{"self":[{"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/posts\/66262","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/comments?post=66262"}],"version-history":[{"count":0,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/posts\/66262\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/media\/66263"}],"wp:attachment":[{"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/media?parent=66262"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/categories?post=66262"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/tags?post=66262"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}