Transcriptomic profiles of neoantigen-reactive T cells in human gastrointestinal cancers

Chunhong Zheng; Joseph N. Fass; Yi Ping Shih; Andrew J. Gunderson; Nelson Sanjuan Silva; Huayu Huang; Brady M. Bernard; Venkatesh Rajamanickam; Joseph Slagel; Carlo B. Bifulco; Brian Piening; Pippa H.A. Newell; Paul D. Hansen; Eric Tran

doi:10.1016/j.ccell.2022.03.005

Transcriptomic profiles of neoantigen-reactive T cells in human gastrointestinal cancers

Chunhong Zheng, Joseph N. Fass, Yi Ping Shih, Andrew J. Gunderson, Nelson Sanjuan Silva, Huayu Huang, Brady M. Bernard, Venkatesh Rajamanickam, Joseph Slagel, Carlo B. Bifulco, Brian Piening, Pippa H.A. Newell, Paul D. Hansen, Eric Tran

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

52 Scopus citations

Abstract

Tumor-infiltrating neoantigen-reactive T cells can mediate regression of metastatic gastrointestinal cancers yet remain poorly characterized. We performed immunological screening against personalized neoantigens in combination with single-cell RNA sequencing on tumor-infiltrating lymphocytes from bile duct and pancreatic cancer patients to characterize the transcriptomic landscape of neoantigen-reactive T cells. We found that most neoantigen-reactive CD8⁺ T cells displayed an exhausted state with significant CXCL13 and GZMA co-expression compared with non-neoantigen-reactive bystander cells. Most neoantigen-reactive CD4⁺ T cells from a patient with bile duct cancer also exhibited an exhausted phenotype but with overexpression of HOPX or ADGRG1 while lacking IL7R expression. Thus, neoantigen-reactive T cells infiltrating gastrointestinal cancers harbor distinct transcriptomic signatures, which may provide new opportunities for harnessing these cells for therapy.

Original language	English
Pages (from-to)	410-423.e7
Journal	Cancer Cell
Volume	40
Issue number	4
DOIs	https://doi.org/10.1016/j.ccell.2022.03.005
State	Published - Apr 11 2022

Keywords

adoptive cell therapy
bile duct cancer
cancer immunotherapy
gastrointestinal cancers
neoantigen
pancreatic cancer
single-cell RNA-seq
tumor-infiltrating lymphocytes

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10.1016/j.ccell.2022.03.005

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Zheng, C., Fass, J. N., Shih, Y. P., Gunderson, A. J., Sanjuan Silva, N., Huang, H., Bernard, B. M., Rajamanickam, V., Slagel, J., Bifulco, C. B., Piening, B., Newell, P. H. A., Hansen, P. D., & Tran, E. (2022). Transcriptomic profiles of neoantigen-reactive T cells in human gastrointestinal cancers. Cancer Cell, 40(4), 410-423.e7. https://doi.org/10.1016/j.ccell.2022.03.005

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title = "Transcriptomic profiles of neoantigen-reactive T cells in human gastrointestinal cancers",

abstract = "Tumor-infiltrating neoantigen-reactive T cells can mediate regression of metastatic gastrointestinal cancers yet remain poorly characterized. We performed immunological screening against personalized neoantigens in combination with single-cell RNA sequencing on tumor-infiltrating lymphocytes from bile duct and pancreatic cancer patients to characterize the transcriptomic landscape of neoantigen-reactive T cells. We found that most neoantigen-reactive CD8+ T cells displayed an exhausted state with significant CXCL13 and GZMA co-expression compared with non-neoantigen-reactive bystander cells. Most neoantigen-reactive CD4+ T cells from a patient with bile duct cancer also exhibited an exhausted phenotype but with overexpression of HOPX or ADGRG1 while lacking IL7R expression. Thus, neoantigen-reactive T cells infiltrating gastrointestinal cancers harbor distinct transcriptomic signatures, which may provide new opportunities for harnessing these cells for therapy.",

keywords = "adoptive cell therapy, bile duct cancer, cancer immunotherapy, gastrointestinal cancers, neoantigen, pancreatic cancer, single-cell RNA-seq, tumor-infiltrating lymphocytes",

author = "Chunhong Zheng and Fass, {Joseph N.} and Shih, {Yi Ping} and Gunderson, {Andrew J.} and {Sanjuan Silva}, Nelson and Huayu Huang and Bernard, {Brady M.} and Venkatesh Rajamanickam and Joseph Slagel and Bifulco, {Carlo B.} and Brian Piening and Newell, {Pippa H.A.} and Hansen, {Paul D.} and Eric Tran",

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year = "2022",

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doi = "10.1016/j.ccell.2022.03.005",

language = "English",

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AU - Zheng, Chunhong

AU - Fass, Joseph N.

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AU - Gunderson, Andrew J.

AU - Sanjuan Silva, Nelson

AU - Huang, Huayu

AU - Bernard, Brady M.

AU - Rajamanickam, Venkatesh

AU - Slagel, Joseph

AU - Bifulco, Carlo B.

AU - Piening, Brian

AU - Newell, Pippa H.A.

AU - Hansen, Paul D.

AU - Tran, Eric

PY - 2022/4/11

Y1 - 2022/4/11

N2 - Tumor-infiltrating neoantigen-reactive T cells can mediate regression of metastatic gastrointestinal cancers yet remain poorly characterized. We performed immunological screening against personalized neoantigens in combination with single-cell RNA sequencing on tumor-infiltrating lymphocytes from bile duct and pancreatic cancer patients to characterize the transcriptomic landscape of neoantigen-reactive T cells. We found that most neoantigen-reactive CD8+ T cells displayed an exhausted state with significant CXCL13 and GZMA co-expression compared with non-neoantigen-reactive bystander cells. Most neoantigen-reactive CD4+ T cells from a patient with bile duct cancer also exhibited an exhausted phenotype but with overexpression of HOPX or ADGRG1 while lacking IL7R expression. Thus, neoantigen-reactive T cells infiltrating gastrointestinal cancers harbor distinct transcriptomic signatures, which may provide new opportunities for harnessing these cells for therapy.

AB - Tumor-infiltrating neoantigen-reactive T cells can mediate regression of metastatic gastrointestinal cancers yet remain poorly characterized. We performed immunological screening against personalized neoantigens in combination with single-cell RNA sequencing on tumor-infiltrating lymphocytes from bile duct and pancreatic cancer patients to characterize the transcriptomic landscape of neoantigen-reactive T cells. We found that most neoantigen-reactive CD8+ T cells displayed an exhausted state with significant CXCL13 and GZMA co-expression compared with non-neoantigen-reactive bystander cells. Most neoantigen-reactive CD4+ T cells from a patient with bile duct cancer also exhibited an exhausted phenotype but with overexpression of HOPX or ADGRG1 while lacking IL7R expression. Thus, neoantigen-reactive T cells infiltrating gastrointestinal cancers harbor distinct transcriptomic signatures, which may provide new opportunities for harnessing these cells for therapy.

KW - adoptive cell therapy

KW - bile duct cancer

KW - cancer immunotherapy

KW - gastrointestinal cancers

KW - neoantigen

KW - pancreatic cancer

KW - single-cell RNA-seq

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VL - 40

SP - 410-423.e7

JO - Cancer Cell

JF - Cancer Cell

IS - 4

ER -

Transcriptomic profiles of neoantigen-reactive T cells in human gastrointestinal cancers

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Keywords

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