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 - 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.
KW - Chemoradiotherapy
KW - Female
KW - Human papillomavirus 16
KW - Humans
KW - Oncogene Proteins, Viral
KW - Papillomavirus E7 Proteins
KW - Papillomavirus Infections
KW - Prognosis
KW - Repressor Proteins
KW - T-Lymphocytes
KW - Tumor Microenvironment
KW - Uterine Cervical Neoplasms
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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
SN - 2326-6066
VL - 10
SP - 259
EP - 271
JO - Cancer immunology research
JF - Cancer immunology research
IS - 2
ER -