Neoantigen-specific CD4(+) T cells in human melanoma have diverse differentiation states and correlate with CD8(+) T cell, macrophage, and B cell function.
Neoantigen-specific CD4(+) T cells in human melanoma have diverse differentiation states and correlate with CD8(+) T cell, macrophage, and B cell function.
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人类黑色素瘤中的新抗原特异性 CD4( ) T 细胞具有不同的分化状态，并与 CD8( ) T 细胞、巨噬细胞和 B 细胞功能相关。
DOI：
10.1016/j.ccell.2022.03.006
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发表时间：
2022-04-11
期刊：
影响因子：
50.3
通讯作者：
Riddell, Stanley R.
中科院分区：
文献类型：
--
作者：
Veatch, Joshua R.;Lee, Sylvia M.;Shasha, Carolyn;Singhi, Naina;Szeto, Julia L.;Moshiri, Ata S.;Kim, Teresa S.;Smythe, Kimberly;Kong, Paul;Fitzgibbon, Matthew;Jesernig, Brenda;Bhatia, Shailender;Tykodi, Scott S.;Hall, Evan T.;Byrd, David R.;Thompson, John A.;Pillarisetty, Venu G.;Duhen, Thomas;Houghton, A. McGarry;Newell, Evan;Gottardo, Raphael;Riddell, Stanley R.
在小鼠模型中，识别肿瘤抗原的 CD4+ T 细胞是免疫检查点抑制剂发挥功效所必需的，但它们在人类癌症中的作用尚不清楚。我们使用单细胞 RNA 测序和 T 细胞受体序列来识别浸润人类黑色素瘤的肿瘤特异性 CD4+ T 细胞的特征和功能相关性。识别肿瘤新抗原的常规 CD4+ T 细胞表达 CXCL13，并细分为表达记忆和 T 滤泡辅助标记物的簇，以及表达细胞溶解标记物、抑制性受体和 IFN-γ 的簇。肿瘤中 CXCL13+ CD4+ T 细胞的频率与 CD8+ T 细胞和巨噬细胞的转录状态、B 细胞的成熟和患者生存相关。在乳腺癌队列中也观察到类似的相关性。这些结果鉴定了黑色素瘤中肿瘤特异性 CD4+ T 细胞的表型和功能相关性，并表明使用此类细胞来改变肿瘤微环境的可能性。
CD4+ T cells that recognize tumor antigens are required for immune checkpoint inhibitor efficacy in murine models but their contributions in human cancer are unclear. We used single cell RNA sequencing and T cell receptor sequences to identify signatures and functional correlates of tumor specific CD4+ T cells infiltrating human melanoma. Conventional CD4+ T cells that recognize tumor neoantigens express CXCL13 and are subdivided into clusters expressing memory and T follicular helper markers, and those expressing cytolytic markers, inhibitory receptors, and IFN-γ. The frequency of CXCL13+ CD4+ T cells in the tumor correlated with the transcriptional states of CD8+ T cells and macrophages, maturation of B cells, and patient survival. Similar correlations were observed in a breast cancer cohort. These results identify phenotypes and functional correlates of tumor specific CD4+ T cells in melanoma and suggest the possibility of using such cells to modify the tumor microenvironment.
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影响因子：
64.8
作者：
Helmink BA;Reddy SM;Gao J;Zhang S;Basar R;Thakur R;Yizhak K;Sade-Feldman M;Blando J;Han G;Gopalakrishnan V;Xi Y;Zhao H;Amaria RN;Tawbi HA;Cogdill AP;Liu W;LeBleu VS;Kugeratski FG;Patel S;Davies MA;Hwu P;Lee JE;Gershenwald JE;Lucci A;Arora R;Woodman S;Keung EZ;Gaudreau PO;Reuben A;Spencer CN;Burton EM;Haydu LE;Lazar AJ;Zapassodi R;Hudgens CW;Ledesma DA;Ong S;Bailey M;Warren S;Rao D;Krijgsman O;Rozeman EA;Peeper D;Blank CU;Schumacher TN;Butterfield LH;Zelazowska MA;McBride KM;Kalluri R;Allison J;Petitprez F;Fridman WH;Sautès-Fridman C;Hacohen N;Rezvani K;Sharma P;Tetzlaff MT;Wang L;Wargo JA
通讯作者：
Wargo JA
影响因子：
64.5
作者：
Cui C;Wang J;Fagerberg E;Chen PM;Connolly KA;Damo M;Cheung JF;Mao T;Askari AS;Chen S;Fitzgerald B;Foster GG;Eisenbarth SC;Zhao H;Craft J;Joshi NS
通讯作者：
Joshi NS
影响因子：
14.9
作者：
Colaprico A;Silva TC;Olsen C;Garofano L;Cava C;Garolini D;Sabedot TS;Malta TM;Pagnotta SM;Castiglioni I;Ceccarelli M;Bontempi G;Noushmehr H
通讯作者：
Noushmehr H
影响因子：
24.8
作者：
Ahmadzadeh, Mojgan;Pasetto, Anna;Rosenberg, Steven A.
通讯作者：
Rosenberg, Steven A.
影响因子：
158.5
作者：
Hunder, Naomi N.;Wallen, Herschel;Yee, Cassian
通讯作者：
Yee, Cassian