Persistent viral infections and tumors pose a major challenge to the immune system. Unlike acute infections, where immune cells rapidly eliminate the pathogen and create protective memory, chronic diseases profoundly transform CD8 T cells, which are essential for fighting infected or cancerous cells. These cells, subjected to prolonged antigenic stimulation, enter an adaptive state called exhaustion. This state is characterized by a gradual loss of their ability to destroy target cells, reduced proliferation, and the sustained expression of inhibitory receptors on their surface.<\/p>\n
The exhaustion of T cells is not simply an immune failure but an adaptive response that limits both excessive inflammation and disease progression. Exhausted cells retain some ability to control infection or tumor growth, albeit in a weakened manner. Their function is regulated by specific transcriptional and epigenetic factors, such as TOX and NR4A, which alter their metabolism and activity. Not all exhausted cells are the same: some, called “stem-like,” retain the ability to self-renew and respond to therapies, while others, more differentiated, lose almost all function.<\/p>\n
Therapies using immune checkpoint inhibitors, such as those targeting PD-1 or CTLA-4, exploit this plasticity. They help revitalize certain exhausted cells, particularly stem-like cells, thereby improving the immune response against tumors or viruses. However, responses often remain partial or temporary, highlighting the need to better understand the underlying mechanisms to develop more effective treatments.<\/p>\n
In chronic infections such as HIV, hepatitis B, or C, virus-specific T cells show similar signs of exhaustion, with increased expression of inhibitory receptors and a reduced ability to eliminate infected cells. Tumors, on the other hand, create a hostile environment where immune cells are deprived of nutrients and overwhelmed by suppressive signals. Despite these obstacles, exhausted T cells remain a prime target for immunotherapies, as their reactivation can restore part of the antitumor response.<\/p>\n
Recent advances reveal that T cell exhaustion is a dynamic and, to some extent, reversible process. Future therapeutic strategies will need to target not only exhausted cells but also their microenvironment to promote lasting immunity while limiting side effects. The stakes are high: transforming these adapted cells into effective allies against chronic diseases and cancers.<\/p>\n
DOI:<\/strong> https:\/\/doi.org\/10.1038\/s41423-026-01405-y<\/a><\/p>\n Title:<\/strong> T cell adaptation in chronic infections and tumors<\/p>\n Journal:<\/strong> Cellular & Molecular Immunology<\/p>\n Publisher:<\/strong> Springer Science and Business Media LLC<\/p>\n Authors:<\/strong> Hendrik Luxenburger; Robert Thimme; Maike Hofmann<\/p>\n","protected":false},"excerpt":{"rendered":" Why Do Immune Cells Become Exhausted in the Face of Chronic Infections and Cancers? Persistent viral infections and tumors pose a major challenge to the immune system. Unlike acute infections, where immune cells rapidly eliminate the pathogen and create protective memory, chronic diseases profoundly transform CD8 T cells, which are essential for fighting infected or… Continue reading Why Do Immune Cells Become Exhausted in the Face of Chronic Infections and Cancers?<\/span><\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[3,2],"tags":[],"class_list":["post-59","post","type-post","status-publish","format-standard","hentry","category-environment","category-health","entry"],"_links":{"self":[{"href":"https:\/\/biologistjournal.com\/en\/wp-json\/wp\/v2\/posts\/59","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/biologistjournal.com\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/biologistjournal.com\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/biologistjournal.com\/en\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/biologistjournal.com\/en\/wp-json\/wp\/v2\/comments?post=59"}],"version-history":[{"count":1,"href":"https:\/\/biologistjournal.com\/en\/wp-json\/wp\/v2\/posts\/59\/revisions"}],"predecessor-version":[{"id":60,"href":"https:\/\/biologistjournal.com\/en\/wp-json\/wp\/v2\/posts\/59\/revisions\/60"}],"wp:attachment":[{"href":"https:\/\/biologistjournal.com\/en\/wp-json\/wp\/v2\/media?parent=59"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/biologistjournal.com\/en\/wp-json\/wp\/v2\/categories?post=59"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/biologistjournal.com\/en\/wp-json\/wp\/v2\/tags?post=59"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}