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

共 56 条

[1] Endogenous Glucocorticoid Signaling Regulates CD8+T Cell Differentiation and Development of Dysfunction in the Tumor Microenvironment [J].

Acharya, Nandini ;

Madi, Asaf ;

Zhang, Huiyuan ;

Klapholz, Max ;

Escobar, Giulia ;

Dulberg, Shai ;

Christian, Elena ;

Ferreira, Michelle ;

Dixon, Karen O. ;

Fell, Geoffrey ;

Tooley, Katherine ;

Mangani, Davide ;

Xia, Junrong ;

Singer, Meromit ;

Bosenberg, Marcus ;

Neuberg, Donna ;

Rozenblatt-Rosen, Orit ;

Regev, Aviv ;

Kuchroo, Vijay K. ;

Anderson, Ana C. .

IMMUNITY, 2020, 53 (03) :658-+

[2] The mitochondrial fission factor dynamin-related protein 1 modulates T-cell receptor signalling at the immune synapse [J].

Baixauli, Francesc ;

Martin-Cofreces, Noa B. ;

Morlino, Giulia ;

Carrasco, Yolanda R. ;

Calabia-Linares, Carmen ;

Veiga, Esteban ;

Serrador, Juan M. ;

Sanchez-Madrid, Francisco .

EMBO JOURNAL, 2011, 30 (07) :1238-1250

[3] Defining 'T cell exhaustion' [J].

Blank, Christian U. ;

Haining, W. Nicholas ;

Held, Werner ;

Hogan, Patrick G. ;

Kallies, Axel ;

Lugli, Enrico ;

Lynn, Rachel C. ;

Philip, Mary ;

Rao, Anjana ;

Restifo, Nicholas P. ;

Schietinger, Andrea ;

Schumacher, Ton N. ;

Schwartzberg, Pamela L. ;

Sharpe, Arlene H. ;

Speiser, Daniel E. ;

Wherry, E. John ;

Youngblood, Benjamin A. ;

Zehn, Dietmar .

NATURE REVIEWS IMMUNOLOGY, 2019, 19 (11) :665-674

[4] Transcriptional programs of neoantigen-specific TIL in anti-PD-1-treated lung cancers [J].

Caushi, Justina X. ;

Zhang, Jiajia ;

Ji, Zhicheng ;

Vaghasia, Ajay ;

Zhang, Boyang ;

Hsiue, Emily Han-Chung ;

Mog, Brian J. ;

Hou, Wenpin ;

Justesen, Sune ;

Blosser, Richard ;

Tam, Ada ;

Anagnostou, Valsamo ;

Cottrell, Tricia R. ;

Guo, Haidan ;

Chan, Hok Yee ;

Singh, Dipika ;

Thapa, Sampriti ;

Dykema, Arbor G. ;

Burman, Poromendro ;

Choudhury, Begum ;

Aparicio, Luis ;

Cheung, Laurene S. ;

Lanis, Mara ;

Belcaid, Zineb ;

El Asmar, Margueritta ;

Illei, Peter B. ;

Wang, Rulin ;

Meyers, Jennifer ;

Schuebel, Kornel ;

Gupta, Anuj ;

Skaist, Alyza ;

Wheelan, Sarah ;

Naidoo, Jarushka ;

Marrone, Kristen A. ;

Brock, Malcolm ;

Ha, Jinny ;

Bush, Errol L. ;

Park, Bernard J. ;

Bott, Matthew ;

Jones, David R. ;

Reuss, Joshua E. ;

Velculescu, Victor E. ;

Chaft, Jamie E. ;

Kinzler, Kenneth W. ;

Zhou, Shibin ;

Vogelstein, Bert ;

Taube, Janis M. ;

Hellmann, Matthew D. ;

Brahmer, Julie R. ;

Merghoub, Taha .

NATURE, 2021, 596 (7870) :126-+

[5] CD8+ CD103+ Tumor-Infiltrating Lymphocytes Are Tumor-Specific Tissue-Resident Memory T Cells and a Prognostic Factor for Survival in Lung Cancer Patients [J].

Djenidi, Faycal ;

Adam, Julien ;

Goubar, Aicha ;

Durgeau, Aurelie ;

Meurice, Guillaume ;

de Montpreville, Vincent ;

Validire, Pierre ;

Besse, Benjamin ;

Mami-Chouaib, Fathia .

JOURNAL OF IMMUNOLOGY, 2015, 194 (07) :3475-3486

[6] Co-expression of CD39 and CD103 identifies tumor-reactive CD8 T cells in human solid tumors [J].

Duhen, Thomas ;

Duhen, Rebekka ;

Montler, Ryan ;

Moses, Jake ;

Moudgil, Tarsem ;

de Miranda, Noel F. ;

Goodall, Cheri P. ;

Blair, Tiffany C. ;

Fox, Bernard A. ;

McDermott, Jason E. ;

Chang, Shu-Ching ;

Grunkemeier, Gary ;

Leidner, Rom ;

Bell, Richard Bryan ;

Weinberg, Andrew D. .

NATURE COMMUNICATIONS, 2018, 9

[7] Functional significance of U2AF1 S34F mutations in lung adenocarcinomas [J].

Esfahani, Mohammad S. ;

Lee, Luke J. ;

Jeon, Young-Jun ;

Flynn, Ryan A. ;

Stehr, Henning ;

Hui, Angela B. ;

Ishisoko, Noriko ;

Kildebeck, Eric ;

Newman, Aaron M. ;

Bratman, Scott V. ;

Porteus, Matthew H. ;

Chang, Howard Y. ;

Alizadeh, Ash A. ;

Diehn, Maximilian .

NATURE COMMUNICATIONS, 2019, 10 (1)

[8] MAST: a flexible statistical framework for assessing transcriptional changes and characterizing heterogeneity in single-cell RNA sequencing data [J].

Finak, Greg ;

McDavid, Andrew ;

Yajima, Masanao ;

Deng, Jingyuan ;

Gersuk, Vivian ;

Shalek, Alex K. ;

Slichter, Chloe K. ;

Miller, Hannah W. ;

McElrath, M. Juliana ;

Prlic, Martin ;

Linsley, Peter S. ;

Gottardo, Raphael .

GENOME BIOLOGY, 2015, 16

[9]

Greitemann J., 2019, ACM Trans. Intell. Syst. Technol., V99, P1, DOI DOI 10.1145/3298981

[10] Prospective identification of neoantigen-specific lymphocytes in the peripheral blood of melanoma patients [J].

Gros, Alena ;

Parkhurst, Maria R. ;

Tran, Eric ;

Pasetto, Anna ;

Robbins, Paul F. ;

Ilyas, Sadia ;

Prickett, Todd D. ;

Gartner, Jared J. ;

Crystal, Jessica S. ;

Roberts, Ilana M. ;

Trebska-McGowan, Kasia ;

Wunderlich, John R. ;

Yang, James C. ;

Rosenberg, Steven A. .

NATURE MEDICINE, 2016, 22 (04) :433-+

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