التفاصيل البيبلوغرافية
| العنوان: |
Unleashing Type-2 Dendritic Cells to Drive Protective Antitumor CD4+ T Cell Immunity. |
| المؤلفون: |
Binnewies, Mikhail1, Mujal, Adriana M.1, Pollack, Joshua L.2, Combes, Alexis J.1,3, Hardison, Emily A.1, Barry, Kevin C.1,3, Tsui, Jessica1,3, Ruhland, Megan K.1, Kersten, Kelly1, Abushawish, Marwan A.2, Spasic, Marko4, Giurintano, Jonathan P.5, Chan, Vincent1,3, Daud, Adil I.4, Ha, Patrick5, Ye, Chun J.6, Roberts, Edward W.1, Krummel, Matthew F.1,3 matthew.krummel@ucsf.edu |
| المصدر: |
Cell. Apr2019, Vol. 177 Issue 3, p556-556. 1p. |
| مصطلحات موضوعية: |
*DENDRITIC cells, *ANTINEOPLASTIC agents, *T cell differentiation, *CD4 antigen, *CANCER treatment |
| مستخلص: |
Differentiation of proinflammatory CD4+ conventional T cells (T conv) is critical for productive antitumor responses yet their elicitation remains poorly understood. We comprehensively characterized myeloid cells in tumor draining lymph nodes (tdLN) of mice and identified two subsets of conventional type-2 dendritic cells (cDC2) that traffic from tumor to tdLN and present tumor-derived antigens to CD4+ T conv , but then fail to support antitumor CD4+ T conv differentiation. Regulatory T cell (T reg) depletion enhanced their capacity to elicit strong CD4+ T conv responses and ensuing antitumor protection. Analogous cDC2 populations were identified in patients, and as in mice, their abundance relative to T reg predicts protective ICOS+ PD-1lo CD4+ T conv phenotypes and survival. Further, in melanoma patients with low T reg abundance, intratumoral cDC2 density alone correlates with abundant CD4+ T conv and with responsiveness to anti-PD-1 therapy. Together, this highlights a pathway that restrains cDC2 and whose reversal enhances CD4+ T conv abundance and controls tumor growth. • cDC2 initiate activation but not differentiation of antitumor CD4+ T conv • T reg depletion relieves cDC2 suppression driving antitumor CD4+ T conv differentiation • Human equivalent of mouse cDC2 are present in the tumor and draining lymph node • The balance of human cDC2/T reg in the TME dictates T cell quality and prognosis A subtype of conventional dendritic cells, cDC2, are able to prime CD4+ T cells for antitumor functions and the presence of cDC2 in human cancer samples may serve as a predictive biomarker for survival and response to immune checkpoint blockade. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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