Tumor recognition and self-recognition induce distinct transcriptional profiles in antigen-specific CD4 T cells

Derese Getnet; Charles H. Maris; Edward L. Hipkiss; Joseph F. Grosso; Timothy J. Harris; Hung Rong Yen; Tullia C. Bruno; Satoshi Wada; Adam Adler; Robert W. Georgantas; Chunfa Charles Jie; Monica V. Goldberg; Drew M. Pardoll; Charles G. Drake

doi:10.4049/jimmunol.0803400

Tumor recognition and self-recognition induce distinct transcriptional profiles in antigen-specific CD4 T cells

Derese Getnet, Charles H. Maris, Edward L. Hipkiss, Joseph F. Grosso, Timothy J. Harris, Hung Rong Yen, Tullia C. Bruno, Satoshi Wada, Adam Adler, Robert W. Georgantas, Chunfa Charles Jie, Monica V. Goldberg, Drew M. Pardoll, Charles G. Drake

School of Medicine

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

32 Scopus citations

Abstract

Tumors express a wide variety of both mutated and nonmutated Ags. Whether these tumor Ags are broadly recognized as self or foreign by the immune system is currently unclear. Using an autochthonous prostate cancer model in which hemagglutinin (HA) is specifically expressed in the tumor (ProHA x TRAMP mice), as well as an analogous model wherein HA is expressed in normal tissues as a model self-Ag (C3HA^high), we examined the transcriptional profile of CD4 T cells undergoing Ag-specific division. Consistent with our previous data, transfer of Ag-specific CD4 T cells into C3HA^high resulted in a functionally inactivated CD4 T cell profile. Conversely, adoptive transfer of an identical CD4 T cell population into ProHA x TRAMP mice resulted in the induction of a regulatory phenotype of the T cell (Treg) both at the transcriptional and functional level. Interestingly, this Treg skewing was a property of even early-stage tumors, suggesting Treg induction as an important tolerance mechanism during tumor development.

Original language	English (US)
Pages (from-to)	4675-4685
Number of pages	11
Journal	Journal of Immunology
Volume	182
Issue number	8
DOIs	https://doi.org/10.4049/jimmunol.0803400
State	Published - Apr 15 2009

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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Getnet, D., Maris, C. H., Hipkiss, E. L., Grosso, J. F., Harris, T. J., Yen, H. R., Bruno, T. C., Wada, S., Adler, A., Georgantas, R. W., Jie, C. C., Goldberg, M. V., Pardoll, D. M., & Drake, C. G. (2009). Tumor recognition and self-recognition induce distinct transcriptional profiles in antigen-specific CD4 T cells. Journal of Immunology, 182(8), 4675-4685. https://doi.org/10.4049/jimmunol.0803400

Getnet, D, Maris, CH, Hipkiss, EL, Grosso, JF, Harris, TJ, Yen, HR, Bruno, TC, Wada, S, Adler, A, Georgantas, RW, Jie, CC, Goldberg, MV, Pardoll, DM & Drake, CG 2009, 'Tumor recognition and self-recognition induce distinct transcriptional profiles in antigen-specific CD4 T cells', Journal of Immunology, vol. 182, no. 8, pp. 4675-4685. https://doi.org/10.4049/jimmunol.0803400

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title = "Tumor recognition and self-recognition induce distinct transcriptional profiles in antigen-specific CD4 T cells",

abstract = "Tumors express a wide variety of both mutated and nonmutated Ags. Whether these tumor Ags are broadly recognized as self or foreign by the immune system is currently unclear. Using an autochthonous prostate cancer model in which hemagglutinin (HA) is specifically expressed in the tumor (ProHA x TRAMP mice), as well as an analogous model wherein HA is expressed in normal tissues as a model self-Ag (C3HAhigh), we examined the transcriptional profile of CD4 T cells undergoing Ag-specific division. Consistent with our previous data, transfer of Ag-specific CD4 T cells into C3HAhigh resulted in a functionally inactivated CD4 T cell profile. Conversely, adoptive transfer of an identical CD4 T cell population into ProHA x TRAMP mice resulted in the induction of a regulatory phenotype of the T cell (Treg) both at the transcriptional and functional level. Interestingly, this Treg skewing was a property of even early-stage tumors, suggesting Treg induction as an important tolerance mechanism during tumor development.",

author = "Derese Getnet and Maris, {Charles H.} and Hipkiss, {Edward L.} and Grosso, {Joseph F.} and Harris, {Timothy J.} and Yen, {Hung Rong} and Bruno, {Tullia C.} and Satoshi Wada and Adam Adler and Georgantas, {Robert W.} and Jie, {Chunfa Charles} and Goldberg, {Monica V.} and Pardoll, {Drew M.} and Drake, {Charles G.}",

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AU - Harris, Timothy J.

AU - Yen, Hung Rong

AU - Bruno, Tullia C.

AU - Wada, Satoshi

AU - Adler, Adam

AU - Georgantas, Robert W.

AU - Jie, Chunfa Charles

AU - Goldberg, Monica V.

AU - Pardoll, Drew M.

AU - Drake, Charles G.

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Tumor recognition and self-recognition induce distinct transcriptional profiles in antigen-specific CD4 T cells

Abstract

ASJC Scopus subject areas

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