Phenotypic signatures of circulating neoantigen-reactive CD8+ T cells in patients with metastatic cancers

Rami Yossef; Sri Krishna; Sivasish Sindiri; Frank J. Lowery; Amy R. Copeland; Jared J. Gartner; Maria R. Parkhurst; Neilesh B. Parikh; Kyle J. Hitscherich; Shoshana T. Levi; Praveen D. Chatani; Nikolaos Zacharakis; Noam Levin; Nolan R. Vale; Shirley K. Nah; Aaron Dinerman; Victoria K. Hill; Satyajit Ray; Alakesh Bera; Lior Levy; Li Jia; Michael C. Kelly; Stephanie L. Goff; Paul F. Robbins; Steven A. Rosenberg

doi:10.1016/j.ccell.2023.11.005

Phenotypic signatures of circulating neoantigen-reactive CD8⁺ T cells in patients with metastatic cancers

Rami Yossef, Sri Krishna, Sivasish Sindiri, Frank J. Lowery, Amy R. Copeland, Jared J. Gartner, Maria R. Parkhurst, Neilesh B. Parikh, Kyle J. Hitscherich, Shoshana T. Levi, Praveen D. Chatani, Nikolaos Zacharakis, Noam Levin, Nolan R. Vale, Shirley K. Nah, Aaron Dinerman, Victoria K. Hill, Satyajit Ray, Alakesh Bera, Lior LevyLi Jia, Michael C. Kelly, Stephanie L. Goff, Paul F. Robbins, Steven A. Rosenberg

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

Abstract

Circulating T cells from peripheral blood (PBL) can provide a rich and noninvasive source for antitumor T cells. By single-cell transcriptomic profiling of 36 neoantigen-specific T cell clones from 6 metastatic cancer patients, we report the transcriptional and cell surface signatures of antitumor PBL-derived CD8⁺ T cells (NeoTCR_PBL). Comparison of tumor-infiltrating lymphocyte (TIL)- and PBL-neoantigen-specific T cells revealed that NeoTCR_PBL T cells are low in frequency and display less-dysfunctional memory phenotypes relative to their TIL counterparts. Analysis of 100 antitumor TCR clonotypes indicates that most NeoTCR_PBL populations target the same neoantigens as TILs. However, NeoTCR_PBL TCR repertoire is only partially shared with TIL. Prediction and testing of NeoTCR_PBL signature-derived TCRs from PBL of 6 prospective patients demonstrate high enrichment of clonotypes targeting tumor mutations, a viral oncogene, and patient-derived tumor. Thus, the NeoTCR_PBL signature provides an alternative source for identifying antitumor T cells from PBL of cancer patients, enabling immune monitoring and immunotherapies.

Original language	English
Pages (from-to)	2154-2165.e5
Journal	Cancer Cell
Volume	41
Issue number	12
DOIs	https://doi.org/10.1016/j.ccell.2023.11.005
State	Published - 11 Dec 2023
Externally published	Yes

Keywords

adoptive cell transfer
blood
CD8 T cells
neoantigens
T cell receptors

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.ccell.2023.11.005

Cite this

Yossef, R., Krishna, S., Sindiri, S., Lowery, F. J., Copeland, A. R., Gartner, J. J., Parkhurst, M. R., Parikh, N. B., Hitscherich, K. J., Levi, S. T., Chatani, P. D., Zacharakis, N., Levin, N., Vale, N. R., Nah, S. K., Dinerman, A., Hill, V. K., Ray, S., Bera, A., ... Rosenberg, S. A. (2023). Phenotypic signatures of circulating neoantigen-reactive CD8⁺ T cells in patients with metastatic cancers. Cancer Cell, 41(12), 2154-2165.e5. https://doi.org/10.1016/j.ccell.2023.11.005

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title = "Phenotypic signatures of circulating neoantigen-reactive CD8+ T cells in patients with metastatic cancers",

abstract = "Circulating T cells from peripheral blood (PBL) can provide a rich and noninvasive source for antitumor T cells. By single-cell transcriptomic profiling of 36 neoantigen-specific T cell clones from 6 metastatic cancer patients, we report the transcriptional and cell surface signatures of antitumor PBL-derived CD8+ T cells (NeoTCRPBL). Comparison of tumor-infiltrating lymphocyte (TIL)- and PBL-neoantigen-specific T cells revealed that NeoTCRPBL T cells are low in frequency and display less-dysfunctional memory phenotypes relative to their TIL counterparts. Analysis of 100 antitumor TCR clonotypes indicates that most NeoTCRPBL populations target the same neoantigens as TILs. However, NeoTCRPBL TCR repertoire is only partially shared with TIL. Prediction and testing of NeoTCRPBL signature-derived TCRs from PBL of 6 prospective patients demonstrate high enrichment of clonotypes targeting tumor mutations, a viral oncogene, and patient-derived tumor. Thus, the NeoTCRPBL signature provides an alternative source for identifying antitumor T cells from PBL of cancer patients, enabling immune monitoring and immunotherapies.",

keywords = "adoptive cell transfer, blood, CD8 T cells, neoantigens, T cell receptors",

author = "Rami Yossef and Sri Krishna and Sivasish Sindiri and Lowery, {Frank J.} and Copeland, {Amy R.} and Gartner, {Jared J.} and Parkhurst, {Maria R.} and Parikh, {Neilesh B.} and Hitscherich, {Kyle J.} and Levi, {Shoshana T.} and Chatani, {Praveen D.} and Nikolaos Zacharakis and Noam Levin and Vale, {Nolan R.} and Nah, {Shirley K.} and Aaron Dinerman and Hill, {Victoria K.} and Satyajit Ray and Alakesh Bera and Lior Levy and Li Jia and Kelly, {Michael C.} and Goff, {Stephanie L.} and Robbins, {Paul F.} and Rosenberg, {Steven A.}",

note = "Publisher Copyright: {\textcopyright} 2023",

year = "2023",

month = dec,

day = "11",

doi = "10.1016/j.ccell.2023.11.005",

language = "English",

volume = "41",

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Yossef, R, Krishna, S, Sindiri, S, Lowery, FJ, Copeland, AR, Gartner, JJ, Parkhurst, MR, Parikh, NB, Hitscherich, KJ, Levi, ST, Chatani, PD, Zacharakis, N, Levin, N, Vale, NR, Nah, SK, Dinerman, A, Hill, VK, Ray, S, Bera, A, Levy, L, Jia, L, Kelly, MC, Goff, SL, Robbins, PF & Rosenberg, SA 2023, 'Phenotypic signatures of circulating neoantigen-reactive CD8⁺ T cells in patients with metastatic cancers', Cancer Cell, vol. 41, no. 12, pp. 2154-2165.e5. https://doi.org/10.1016/j.ccell.2023.11.005

TY - JOUR

T1 - Phenotypic signatures of circulating neoantigen-reactive CD8+ T cells in patients with metastatic cancers

AU - Yossef, Rami

AU - Krishna, Sri

AU - Sindiri, Sivasish

AU - Lowery, Frank J.

AU - Copeland, Amy R.

AU - Gartner, Jared J.

AU - Parkhurst, Maria R.

AU - Parikh, Neilesh B.

AU - Hitscherich, Kyle J.

AU - Levi, Shoshana T.

AU - Chatani, Praveen D.

AU - Zacharakis, Nikolaos

AU - Levin, Noam

AU - Vale, Nolan R.

AU - Nah, Shirley K.

AU - Dinerman, Aaron

AU - Hill, Victoria K.

AU - Ray, Satyajit

AU - Bera, Alakesh

AU - Levy, Lior

AU - Jia, Li

AU - Kelly, Michael C.

AU - Goff, Stephanie L.

AU - Robbins, Paul F.

AU - Rosenberg, Steven A.

PY - 2023/12/11

Y1 - 2023/12/11

N2 - Circulating T cells from peripheral blood (PBL) can provide a rich and noninvasive source for antitumor T cells. By single-cell transcriptomic profiling of 36 neoantigen-specific T cell clones from 6 metastatic cancer patients, we report the transcriptional and cell surface signatures of antitumor PBL-derived CD8+ T cells (NeoTCRPBL). Comparison of tumor-infiltrating lymphocyte (TIL)- and PBL-neoantigen-specific T cells revealed that NeoTCRPBL T cells are low in frequency and display less-dysfunctional memory phenotypes relative to their TIL counterparts. Analysis of 100 antitumor TCR clonotypes indicates that most NeoTCRPBL populations target the same neoantigens as TILs. However, NeoTCRPBL TCR repertoire is only partially shared with TIL. Prediction and testing of NeoTCRPBL signature-derived TCRs from PBL of 6 prospective patients demonstrate high enrichment of clonotypes targeting tumor mutations, a viral oncogene, and patient-derived tumor. Thus, the NeoTCRPBL signature provides an alternative source for identifying antitumor T cells from PBL of cancer patients, enabling immune monitoring and immunotherapies.

AB - Circulating T cells from peripheral blood (PBL) can provide a rich and noninvasive source for antitumor T cells. By single-cell transcriptomic profiling of 36 neoantigen-specific T cell clones from 6 metastatic cancer patients, we report the transcriptional and cell surface signatures of antitumor PBL-derived CD8+ T cells (NeoTCRPBL). Comparison of tumor-infiltrating lymphocyte (TIL)- and PBL-neoantigen-specific T cells revealed that NeoTCRPBL T cells are low in frequency and display less-dysfunctional memory phenotypes relative to their TIL counterparts. Analysis of 100 antitumor TCR clonotypes indicates that most NeoTCRPBL populations target the same neoantigens as TILs. However, NeoTCRPBL TCR repertoire is only partially shared with TIL. Prediction and testing of NeoTCRPBL signature-derived TCRs from PBL of 6 prospective patients demonstrate high enrichment of clonotypes targeting tumor mutations, a viral oncogene, and patient-derived tumor. Thus, the NeoTCRPBL signature provides an alternative source for identifying antitumor T cells from PBL of cancer patients, enabling immune monitoring and immunotherapies.

KW - adoptive cell transfer

KW - blood

KW - CD8 T cells

KW - neoantigens

KW - T cell receptors

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U2 - 10.1016/j.ccell.2023.11.005

DO - 10.1016/j.ccell.2023.11.005

M3 - Article

C2 - 38039963

AN - SCOPUS:85179073342

SN - 1535-6108

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SP - 2154-2165.e5

JO - Cancer Cell

JF - Cancer Cell

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ER -