Expansion of Candidate HPV-Specific T Cells in the Tumor Microenvironment during Chemoradiotherapy Is Prognostic in HPV16 Cancers

Lauren E. Colbert; Molly B. El Alam; Erica J. Lynn; Julianna Bronk; Tatiana V. Karpinets; Xiaogang Wu; Bhavana V. Chapman; Travis T. Sims; Daniel Lin; Ramez Kouzy; Julie Sammouri; Greyson Biegert; Andrea Y.Delgado Medrano; Adilene Olvera; K. Jagannadha Sastry; Patricia J. Eifel; Anuja Jhingran; Lilie Lin; Lois M. Ramondetta; Andrew P. Futreal; Amir A. Jazaeri; Kathleen M. Schmeler; Jingyan Yue; Aparna Mitra; Kyoko Yoshida-Court; Jennifer A. Wargo; Travis N. Solley; Venkatesh Hegde; Sita S. Nookala; Ananta V. Yanamandra; Stephanie Dorta-Estremera; Geena Mathew; Rohit Kavukuntla; Cassidy Papso; Mustapha Ahmed-Kaddar; Minsoo Kim; Jianhua Zhang; Alexandre Reuben; Emma B. Holliday; Bruce D. Minsky; Albert C. Koong; Eugene J. Koay; Prajnan Das; Cullen M. Taniguchi; Ann Klopp

doi:10.1158/2326-6066.CIR-21-0119

Expansion of Candidate HPV-Specific T Cells in the Tumor Microenvironment during Chemoradiotherapy Is Prognostic in HPV16 Cancers

Lauren E. Colbert, Molly B. El Alam, Erica J. Lynn, Julianna Bronk, Tatiana V. Karpinets, Xiaogang Wu, Bhavana V. Chapman, Travis T. Sims, Daniel Lin, Ramez Kouzy, Julie Sammouri, Greyson Biegert, Andrea Y.Delgado Medrano, Adilene Olvera, K. Jagannadha Sastry, Patricia J. Eifel, Anuja Jhingran, Lilie Lin, Lois M. Ramondetta, Andrew P. FutrealAmir A. Jazaeri, Kathleen M. Schmeler, Jingyan Yue, Aparna Mitra, Kyoko Yoshida-Court, Jennifer A. Wargo, Travis N. Solley, Venkatesh Hegde, Sita S. Nookala, Ananta V. Yanamandra, Stephanie Dorta-Estremera, Geena Mathew, Rohit Kavukuntla, Cassidy Papso, Mustapha Ahmed-Kaddar, Minsoo Kim, Jianhua Zhang, Alexandre Reuben, Emma B. Holliday, Bruce D. Minsky, Albert C. Koong, Eugene J. Koay, Prajnan Das, Cullen M. Taniguchi, Ann Klopp

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

2 Scopus citations

Abstract

Human papillomavirus (HPV) infection causes 600,000 new cancers worldwide each year. HPV-related cancers express the oncogenic proteins E6 and E7, which could serve as tumorspecific antigens. It is not known whether immunity to E6 and E7 evolves during chemoradiotherapy or affects survival. Using T cells from 2 HPV16 patients, we conducted functional T-cell assays to identify candidate HPV-specific T cells and common T-cell receptor motifs, which we then analyzed across 86 patients with HPV-related cancers. The HPV-specific clones and E7-related T-cell receptor motifs expanded in the tumor microenvironment over the course of treatment, whereas non-HPV-specific T cells did not. In HPV16 patients, improved recurrence-free survival was associated with HPV-responsive T-cell expansion during chemoradiotherapy.

Original language	English (US)
Pages (from-to)	259-271
Number of pages	13
Journal	Cancer immunology research
Volume	10
Issue number	2
DOIs	https://doi.org/10.1158/2326-6066.CIR-21-0119
State	Published - Feb 2022

ASJC Scopus subject areas

Immunology
Cancer Research

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10.1158/2326-6066.CIR-21-0119

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Colbert, L. E., El Alam, M. B., Lynn, E. J., Bronk, J., Karpinets, T. V., Wu, X., Chapman, B. V., Sims, T. T., Lin, D., Kouzy, R., Sammouri, J., Biegert, G., Medrano, A. Y. D., Olvera, A., Sastry, K. J., Eifel, P. J., Jhingran, A., Lin, L., Ramondetta, L. M., ... Klopp, A. (2022). Expansion of Candidate HPV-Specific T Cells in the Tumor Microenvironment during Chemoradiotherapy Is Prognostic in HPV16 Cancers. Cancer immunology research, 10(2), 259-271. https://doi.org/10.1158/2326-6066.CIR-21-0119

Colbert, LE, El Alam, MB, Lynn, EJ, Bronk, J, Karpinets, TV, Wu, X, Chapman, BV, Sims, TT, Lin, D, Kouzy, R, Sammouri, J, Biegert, G, Medrano, AYD, Olvera, A, Sastry, KJ, Eifel, PJ, Jhingran, A, Lin, L, Ramondetta, LM, Futreal, AP, Jazaeri, AA, Schmeler, KM, Yue, J, Mitra, A, Yoshida-Court, K, Wargo, JA, Solley, TN, Hegde, V, Nookala, SS, Yanamandra, AV, Dorta-Estremera, S, Mathew, G, Kavukuntla, R, Papso, C, Ahmed-Kaddar, M, Kim, M, Zhang, J, Reuben, A, Holliday, EB, Minsky, BD, Koong, AC, Koay, EJ, Das, P, Taniguchi, CM & Klopp, A 2022, 'Expansion of Candidate HPV-Specific T Cells in the Tumor Microenvironment during Chemoradiotherapy Is Prognostic in HPV16 Cancers', Cancer immunology research, vol. 10, no. 2, pp. 259-271. https://doi.org/10.1158/2326-6066.CIR-21-0119

@article{711abfc8270045f69afeb75e560e53f9,

title = "Expansion of Candidate HPV-Specific T Cells in the Tumor Microenvironment during Chemoradiotherapy Is Prognostic in HPV16 Cancers",

abstract = "Human papillomavirus (HPV) infection causes 600,000 new cancers worldwide each year. HPV-related cancers express the oncogenic proteins E6 and E7, which could serve as tumorspecific antigens. It is not known whether immunity to E6 and E7 evolves during chemoradiotherapy or affects survival. Using T cells from 2 HPV16 patients, we conducted functional T-cell assays to identify candidate HPV-specific T cells and common T-cell receptor motifs, which we then analyzed across 86 patients with HPV-related cancers. The HPV-specific clones and E7-related T-cell receptor motifs expanded in the tumor microenvironment over the course of treatment, whereas non-HPV-specific T cells did not. In HPV16 patients, improved recurrence-free survival was associated with HPV-responsive T-cell expansion during chemoradiotherapy.",

author = "Colbert, {Lauren E.} and {El Alam}, {Molly B.} and Lynn, {Erica J.} and Julianna Bronk and Karpinets, {Tatiana V.} and Xiaogang Wu and Chapman, {Bhavana V.} and Sims, {Travis T.} and Daniel Lin and Ramez Kouzy and Julie Sammouri and Greyson Biegert and Medrano, {Andrea Y.Delgado} and Adilene Olvera and Sastry, {K. Jagannadha} and Eifel, {Patricia J.} and Anuja Jhingran and Lilie Lin and Ramondetta, {Lois M.} and Futreal, {Andrew P.} and Jazaeri, {Amir A.} and Schmeler, {Kathleen M.} and Jingyan Yue and Aparna Mitra and Kyoko Yoshida-Court and Wargo, {Jennifer A.} and Solley, {Travis N.} and Venkatesh Hegde and Nookala, {Sita S.} and Yanamandra, {Ananta V.} and Stephanie Dorta-Estremera and Geena Mathew and Rohit Kavukuntla and Cassidy Papso and Mustapha Ahmed-Kaddar and Minsoo Kim and Jianhua Zhang and Alexandre Reuben and Holliday, {Emma B.} and Minsky, {Bruce D.} and Koong, {Albert C.} and Koay, {Eugene J.} and Prajnan Das and Taniguchi, {Cullen M.} and Ann Klopp",

note = "Funding Information: L.E. Colbert reports grants from American Society for Clinical Oncology and MD Anderson Cancer Center during the conduct of the study. E.J. Lynn reports grants from HHS|NIH|NCI during the conduct of the study. A. Olvera reports grants from NIH during the conduct of the study. A. Jhingran reports personal fees from Genentech during the conduct of the study, as well as personal fees from Genentech outside the submitted work. L. Lin reports other support from AstraZeneca and Pfizer, and grants from NCI outside the submitted work. A.A. Jazaeri reports other support from Lovance, Bristol Myers Squibb, AstraZeneca, Aravive, Merck, and Eli Lilly and personal fees from Nuprobe, AvengeBio, Genentech-Roche, EMD-Serono, Agenus, Macrogenics, TwoXAR, and Instil Bio outside the submitted work. J.A. Wargo reports other support from Micronoma during the conduct of the study, as well as other support from Imedex, Dava Oncology, Illumina, and PeerView outside the submitted work. A. Reuben reports scientific advisory board and honoraria from Adaptive Biotechnologies. A.C. Koong is a stockholder in Aravive, Inc. E.J. Koay reports personal fees from Apollo Cancer Center, RenovoRx, Taylor and Francis, and AstraZeneca and grants from NIH, DOD, SU2C, and CPRIT outside the submitted work, as well as a patent for 3D printing of customized oral stents pending. P. Das reports personal fees from Adlai Nortye, NCI, and American Society for Radiation Oncology outside the submitted work. No disclosures were reported by the other authors. Funding Information: This work was supported in part by Cancer Center Support (Core) Grant P30 CA016672 from the NCI, NIH, to The University of Texas MD Anderson Cancer Center, an American Society for Clinical Oncology (ASCO) Young Investigator Award, The University of Texas MD Anderson HPV Moon Shots Program, and a Publisher Copyright: {\textcopyright} 2022 American Association for Cancer Research.",

year = "2022",

month = feb,

doi = "10.1158/2326-6066.CIR-21-0119",

language = "English (US)",

volume = "10",

pages = "259--271",

journal = "Cancer immunology research",

issn = "2326-6066",

publisher = "American Association for Cancer Research Inc.",

number = "2",

}

TY - JOUR

T1 - Expansion of Candidate HPV-Specific T Cells in the Tumor Microenvironment during Chemoradiotherapy Is Prognostic in HPV16 Cancers

AU - Colbert, Lauren E.

AU - El Alam, Molly B.

AU - Lynn, Erica J.

AU - Bronk, Julianna

AU - Karpinets, Tatiana V.

AU - Wu, Xiaogang

AU - Chapman, Bhavana V.

AU - Sims, Travis T.

AU - Lin, Daniel

AU - Kouzy, Ramez

AU - Sammouri, Julie

AU - Biegert, Greyson

AU - Medrano, Andrea Y.Delgado

AU - Olvera, Adilene

AU - Sastry, K. Jagannadha

AU - Eifel, Patricia J.

AU - Jhingran, Anuja

AU - Lin, Lilie

AU - Ramondetta, Lois M.

AU - Futreal, Andrew P.

AU - Jazaeri, Amir A.

AU - Schmeler, Kathleen M.

AU - Yue, Jingyan

AU - Mitra, Aparna

AU - Yoshida-Court, Kyoko

AU - Wargo, Jennifer A.

AU - Solley, Travis N.

AU - Hegde, Venkatesh

AU - Nookala, Sita S.

AU - Yanamandra, Ananta V.

AU - Dorta-Estremera, Stephanie

AU - Mathew, Geena

AU - Kavukuntla, Rohit

AU - Papso, Cassidy

AU - Ahmed-Kaddar, Mustapha

AU - Kim, Minsoo

AU - Zhang, Jianhua

AU - Reuben, Alexandre

AU - Holliday, Emma B.

AU - Minsky, Bruce D.

AU - Koong, Albert C.

AU - Koay, Eugene J.

AU - Das, Prajnan

AU - Taniguchi, Cullen M.

AU - Klopp, Ann

N1 - Funding Information: L.E. Colbert reports grants from American Society for Clinical Oncology and MD Anderson Cancer Center during the conduct of the study. E.J. Lynn reports grants from HHS|NIH|NCI during the conduct of the study. A. Olvera reports grants from NIH during the conduct of the study. A. Jhingran reports personal fees from Genentech during the conduct of the study, as well as personal fees from Genentech outside the submitted work. L. Lin reports other support from AstraZeneca and Pfizer, and grants from NCI outside the submitted work. A.A. Jazaeri reports other support from Lovance, Bristol Myers Squibb, AstraZeneca, Aravive, Merck, and Eli Lilly and personal fees from Nuprobe, AvengeBio, Genentech-Roche, EMD-Serono, Agenus, Macrogenics, TwoXAR, and Instil Bio outside the submitted work. J.A. Wargo reports other support from Micronoma during the conduct of the study, as well as other support from Imedex, Dava Oncology, Illumina, and PeerView outside the submitted work. A. Reuben reports scientific advisory board and honoraria from Adaptive Biotechnologies. A.C. Koong is a stockholder in Aravive, Inc. E.J. Koay reports personal fees from Apollo Cancer Center, RenovoRx, Taylor and Francis, and AstraZeneca and grants from NIH, DOD, SU2C, and CPRIT outside the submitted work, as well as a patent for 3D printing of customized oral stents pending. P. Das reports personal fees from Adlai Nortye, NCI, and American Society for Radiation Oncology outside the submitted work. No disclosures were reported by the other authors. Funding Information: This work was supported in part by Cancer Center Support (Core) Grant P30 CA016672 from the NCI, NIH, to The University of Texas MD Anderson Cancer Center, an American Society for Clinical Oncology (ASCO) Young Investigator Award, The University of Texas MD Anderson HPV Moon Shots Program, and a Publisher Copyright: © 2022 American Association for Cancer Research.

PY - 2022/2

Y1 - 2022/2

N2 - Human papillomavirus (HPV) infection causes 600,000 new cancers worldwide each year. HPV-related cancers express the oncogenic proteins E6 and E7, which could serve as tumorspecific antigens. It is not known whether immunity to E6 and E7 evolves during chemoradiotherapy or affects survival. Using T cells from 2 HPV16 patients, we conducted functional T-cell assays to identify candidate HPV-specific T cells and common T-cell receptor motifs, which we then analyzed across 86 patients with HPV-related cancers. The HPV-specific clones and E7-related T-cell receptor motifs expanded in the tumor microenvironment over the course of treatment, whereas non-HPV-specific T cells did not. In HPV16 patients, improved recurrence-free survival was associated with HPV-responsive T-cell expansion during chemoradiotherapy.

AB - Human papillomavirus (HPV) infection causes 600,000 new cancers worldwide each year. HPV-related cancers express the oncogenic proteins E6 and E7, which could serve as tumorspecific antigens. It is not known whether immunity to E6 and E7 evolves during chemoradiotherapy or affects survival. Using T cells from 2 HPV16 patients, we conducted functional T-cell assays to identify candidate HPV-specific T cells and common T-cell receptor motifs, which we then analyzed across 86 patients with HPV-related cancers. The HPV-specific clones and E7-related T-cell receptor motifs expanded in the tumor microenvironment over the course of treatment, whereas non-HPV-specific T cells did not. In HPV16 patients, improved recurrence-free survival was associated with HPV-responsive T-cell expansion during chemoradiotherapy.

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U2 - 10.1158/2326-6066.CIR-21-0119

DO - 10.1158/2326-6066.CIR-21-0119

M3 - Article

C2 - 35045973

AN - SCOPUS:85124056415

VL - 10

SP - 259

EP - 271

JO - Cancer immunology research

JF - Cancer immunology research

SN - 2326-6066

IS - 2

ER -

Expansion of Candidate HPV-Specific T Cells in the Tumor Microenvironment during Chemoradiotherapy Is Prognostic in HPV16 Cancers

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