FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4383105909> ?p ?o ?g. }

• W4383105909 abstract "ABSTRACT Tumor-reactive CD8 T cells found in cancer patients are frequently dysfunctional, unable to halt tumor growth. Adoptive T cell transfer (ACT), the administration of large numbers of in vitro -generated cytolytic tumor-reactive CD8 T cells, is an important cancer immune therapy being pursued. However, a limitation of ACT is that transferred CD8 T cells often rapidly lose effector function, and despite exciting results in certain malignancies, few ACT clinical trials have shown responses in solid tumors. Here, we developed preclinical cancer mouse models to investigate if and how tumor-specific CD4 T cells can be enlisted to overcome CD8 T cell dysfunction in the setting of ACT. In situ confocal microscopy of color-coded cancer cells, tumor-specific CD8 and CD4 T cells, and antigen presenting cells (APC), combined with functional studies, revealed that the spatial positioning and interactions of CD8 and CD4 T cells, but not their numbers, dictates ACT efficacy and anti-tumor responses. We uncover a new role of antigen-specific CD4 T cells in addition to the known requirement for CD4 T cells during priming/activation of naïve CD8 T cells. CD4 T cells must co-engage with CD8 T cells and APC cross-presenting CD8-and CD4-tumor antigens during the effector phase, forming a three-cell-cluster (triad), to license CD8 T cell cytotoxicity and mediate cancer cell elimination. Triad formation transcriptionally and epigenetically reprogram CD8 T cells, prevent T cell dysfunction/exhaustion, and ultimately lead to the elimination of large established tumors and confer long-term protection from recurrence. When intratumoral triad formation was disrupted, adoptively transferred CD8 T cells could not be reprogrammed, and tumors progressed despite equal numbers of tumor-infiltrating CD8 and CD4 T cells. Strikingly, the formation of CD4 T cell::CD8 T cell::APC triads in tumors of patients with lung cancers treated with immune checkpoint blockade was associated with clinical responses, but not CD4::APC dyads or overall numbers of CD8 or CD4 T cells, demonstrating the importance of triads in non-ACT settings in humans. Our work uncovers intratumoral triads as a key requirement for anti-tumor immunity and a new role for CD4 T cells in CD8 T cell cytotoxicity and cancer cell eradication." @default.
• W4383105909 created "2023-07-05" @default.
• W4383105909 creator A5009332522 @default.
• W4383105909 creator A5023175421 @default.
• W4383105909 creator A5029805571 @default.
• W4383105909 creator A5031892664 @default.
• W4383105909 creator A5039775499 @default.
• W4383105909 creator A5056461166 @default.
• W4383105909 creator A5072909840 @default.
• W4383105909 creator A5074452869 @default.
• W4383105909 creator A5078779601 @default.
• W4383105909 date "2023-07-03" @default.
• W4383105909 modified "2023-09-27" @default.
• W4383105909 title "Intratumoral immune triads are required for adoptive T cell therapy-mediated elimination of solid tumors" @default.
• W4383105909 cites W1444462873 @default.
• W4383105909 cites W1491815146 @default.
• W4383105909 cites W1501518736 @default.
• W4383105909 cites W1524773295 @default.
• W4383105909 cites W1678167583 @default.
• W4383105909 cites W1859254390 @default.
• W4383105909 cites W1933658694 @default.
• W4383105909 cites W1964829509 @default.
• W4383105909 cites W1980621729 @default.
• W4383105909 cites W1984927242 @default.
• W4383105909 cites W1991287153 @default.
• W4383105909 cites W2000297273 @default.
• W4383105909 cites W2006428939 @default.
• W4383105909 cites W2014677321 @default.
• W4383105909 cites W2016671320 @default.
• W4383105909 cites W2021472146 @default.
• W4383105909 cites W2021750859 @default.
• W4383105909 cites W2042699075 @default.
• W4383105909 cites W2043904711 @default.
• W4383105909 cites W2046161326 @default.
• W4383105909 cites W2050899268 @default.
• W4383105909 cites W2051282088 @default.
• W4383105909 cites W2052363929 @default.
• W4383105909 cites W2056346648 @default.
• W4383105909 cites W2063497807 @default.
• W4383105909 cites W2069390977 @default.
• W4383105909 cites W2078710631 @default.
• W4383105909 cites W2080641261 @default.
• W4383105909 cites W2087304127 @default.
• W4383105909 cites W2094652659 @default.
• W4383105909 cites W2103452148 @default.
• W4383105909 cites W2116236834 @default.
• W4383105909 cites W2124799159 @default.
• W4383105909 cites W2132923173 @default.
• W4383105909 cites W2138733343 @default.
• W4383105909 cites W2139640891 @default.
• W4383105909 cites W2140341972 @default.
• W4383105909 cites W2148360952 @default.
• W4383105909 cites W2151246207 @default.
• W4383105909 cites W2151998105 @default.
• W4383105909 cites W2157383025 @default.
• W4383105909 cites W2158187351 @default.
• W4383105909 cites W2162332541 @default.
• W4383105909 cites W2164364292 @default.
• W4383105909 cites W2170830174 @default.
• W4383105909 cites W2188957902 @default.
• W4383105909 cites W2281137630 @default.
• W4383105909 cites W2319534054 @default.
• W4383105909 cites W2406250479 @default.
• W4383105909 cites W2596760231 @default.
• W4383105909 cites W2724264513 @default.
• W4383105909 cites W2728365508 @default.
• W4383105909 cites W2791694787 @default.
• W4383105909 cites W2884754721 @default.
• W4383105909 cites W2947617159 @default.
• W4383105909 cites W2948231422 @default.
• W4383105909 cites W2950413690 @default.
• W4383105909 cites W2951598503 @default.
• W4383105909 cites W2952354682 @default.
• W4383105909 cites W2952815301 @default.
• W4383105909 cites W2966041852 @default.
• W4383105909 cites W2982049472 @default.
• W4383105909 cites W3011649079 @default.
• W4383105909 cites W3022224433 @default.
• W4383105909 cites W3052573234 @default.
• W4383105909 cites W3111462718 @default.
• W4383105909 cites W3175752499 @default.
• W4383105909 cites W3179304282 @default.
• W4383105909 cites W4200422797 @default.
• W4383105909 cites W4311203429 @default.
• W4383105909 cites W4320896665 @default.
• W4383105909 cites W4380786205 @default.
• W4383105909 doi "https://doi.org/10.1101/2023.07.03.547423" @default.
• W4383105909 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37461721" @default.
• W4383105909 hasPublicationYear "2023" @default.
• W4383105909 type Work @default.
• W4383105909 citedByCount "0" @default.
• W4383105909 crossrefType "posted-content" @default.
• W4383105909 hasAuthorship W4383105909A5009332522 @default.
• W4383105909 hasAuthorship W4383105909A5023175421 @default.
• W4383105909 hasAuthorship W4383105909A5029805571 @default.
• W4383105909 hasAuthorship W4383105909A5031892664 @default.
• W4383105909 hasAuthorship W4383105909A5039775499 @default.
• W4383105909 hasAuthorship W4383105909A5056461166 @default.
• W4383105909 hasAuthorship W4383105909A5072909840 @default.
• W4383105909 hasAuthorship W4383105909A5074452869 @default.

• next