A phenotypic signature that identifies neoantigen-reactive T cells in fresh human lung cancers

被引：103

作者：

Hanada, Ken-ichi ^{[1
]}

Zhao, Chihao ^{[1
]}

Gil-Hoyos, Raul ^{[1
]}

Gartner, Jared J. ^{[1
]}

Chow-Parmer, Christopher ^{[1
]}

Lowery, Frank J. ^{[1
]}

Krishna, Sri ^{[1
]}

Prickett, Todd D. ^{[1
]}

Kivitz, Scott ^{[1
]}

Parkhurst, Maria R. ^{[1
]}

Wong, Nathan ^{[2
,3
]}

Rae, Zachary ^{[4
]}

Kelly, Michael C. ^{[4
]}

Goff, Stephanie L. ^{[1
]}

Robbins, Paul F. ^{[1
]}

Rosenberg, Steven A. ^{[1
]}

Yang, James C. ^{[1
]}

机构：

[1] NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA

[2] NCI, CCR Collaborat Bioinformat Resource, Ctr Canc Res, NIH, Bethesda, MD 20892 USA

[3] Frederick Natl Lab Canc Res, Adv Biomed Computat Sci, Leidos Biomed Res, Frederick, MD 21701 USA

[4] Frederick Natl Lab Canc Res, Canc Res Technol Program, Single Cell Anal Facil, Bethesda, MD 20892 USA

来源：

CANCER CELL | 2022年 / 40卷 / 05期

关键词：

TUMOR-INFILTRATING LYMPHOCYTES; PERIPHERAL-BLOOD; PD-1; BLOCKADE; IMMUNOTHERAPY; MELANOMA; ANTIGENS; RECEPTOR; MUTATIONS; LANDSCAPE; TISSUE;

D O I：

10.1016/j.ccell.2022.03.012

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

A common theme across multiple successful immunotherapies for cancer is the recognition of tumor-specific mutations (neoantigens) by T cells. The rapid discovery of such antigen responses could lead to improved therapies through the adoptive transfer of T cells engineered to express neoantigen-reactive T cell receptors (TCRs). Here, through CITE-seq (cellular indexing of transcriptomes and epitopes by sequencing) and TCR-seq of non-small cell lung cancer (NSCLC) tumor-infiltrating lymphocytes (TILs), we develop a neoantigen-reactive T cell signature based on clonotype frequency and CD39 protein and CXCL 13 mRNA expression. Screening of TCRs selected by the signature allows us to identify neoantigen-reactive TCRs with a success rate of 45% for CD8(+) and 66% for CD4(+) T cells. Because of the small number of samples analyzed (4 patients), generalizability remains to be tested. However, this approach can enable the quick identification of neoantigen-reactive TCRs and expedite the engineering of personalized neoantigen-reactive T cells for therapy.

引用

页码：479 / +

页数：22

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