PMID- 32712575
OWN - NLM
STAT- MEDLINE
DCOM- 20210913
LR  - 20210913
IS  - 1879-0593 (Electronic)
IS  - 1368-8375 (Linking)
VI  - 111
DP  - 2020 Dec
TI  - T cell fraction impacts oncologic outcomes in human papillomavirus associated 
      oropharyngeal squamous cell carcinoma.
PG  - 104894
LID - S1368-8375(20)30330-4 [pii]
LID - 10.1016/j.oraloncology.2020.104894 [doi]
AB  - BACKGROUND: We investigated T cell clonality (TCC) and T cell fraction (TCF) in 
      human papilloma virus associated oropharyngeal squamous cell carcinoma 
      (HPV(+)OPSCC) progressors [cases] vs. non-progressors [controls]. METHODS: This 
      nested case-control study included patients undergoing intent-to-cure 
      surgery +/- adjuvant therapy from 6/1/2007-10/3/2016. Patients experiencing 
      local/regional/distant disease (progressors), and a consecutive sample of 
      non-progressors were matched (2 controls: 1 case) on tumor subsite, T-stage and 
      number of metastatic lymph nodes. We performed imunosequencing of the CDR3 
      regions of human TCRbeta chains. RESULTS: 34 progressors and 65 non-progressors were 
      included. There was no statistically significant difference in baseline TCF 
      (range: 0.039-1.084) and TCC (range: 0.007-0.240) (p > 0.05). Female sex was 
      associated with higher TCF (p = 0.03), while extranodal extension (ENE) was 
      associated with lower TCF (p = 0.01). There was a positive correlation between 
      tumor size and clonality (R = 0.34, p < 0.01). The strongest predictor of 
      progression-free survival (PFS) was TCF (HR 0.80, 95%CI 0.66-0.96, p = 0.02). The 
      strongest predictors of cancer specific survival (CSS) were TCF (HR0.69, 95%CI 
      0.47-1.00, p < 0.05) and Adult Comorbidity Evaluation-27 (ACE-27) score 
      (p < 0.05). Similarly, the strongest predictors of overall survival (OS) were TCF 
      (HR 0.62, 95%CI 0.43-0.91, p = 0.01) and ACE-27 score (p = 0.03). On 
      multivariable modeling, TCF >/= 0.4 was independently associated with PFS (HR 0.34, 
      95%CI 0.14-0.85, p = 0.02) while an ACE-27 score of >/= 2 independently predicted 
      CSS (HR 3.85, 95%CI 1.07-13.85, p = 0.04) and OS (HR 3.51, 95%CI 1.10-11.20, 
      p = 0.03). CONCLUSIONS: In patients with HPV(+)OPSCC, TCF was higher in female 
      patients and those without ENE, suggesting differential immune responses. Lower 
      TCF was significantly and independently associated with disease progression. 
      Better ACE-27 scores appear to predict improved oncologic control.
CI  - Copyright (c) 2020 Elsevier Ltd. All rights reserved.
FAU - Van Abel, Kathryn M
AU  - Van Abel KM
AD  - Department of Otolaryngology-Head and Neck Surgery, Mayo Clinic, Rochester, MN 
      55905, USA. Electronic address: vanabel.kathryn@mayo.edu.
FAU - Routman, David M
AU  - Routman DM
AD  - Department of Radiation Oncology, Mayo Clinic, Rochester, MN 55905, USA.
FAU - Moore, Eric J
AU  - Moore EJ
AD  - Department of Otolaryngology-Head and Neck Surgery, Mayo Clinic, Rochester, MN 
      55905, USA.
FAU - Ma, Daniel J
AU  - Ma DJ
AD  - Department of Radiation Oncology, Mayo Clinic, Rochester, MN 55905, USA.
FAU - Yin, Linda X
AU  - Yin LX
AD  - Department of Otolaryngology-Head and Neck Surgery, Mayo Clinic, Rochester, MN 
      55905, USA.
FAU - Fields, Paul A
AU  - Fields PA
AD  - Adaptive Biotechnologies, Seattle, WA 98102, USA; Department of Pathology and 
      Clinical Medicine, Mayo Clinic, Rochester, MN 55905, USA.
FAU - Schofield, Matt
AU  - Schofield M
AD  - Adaptive Biotechnologies, Seattle, WA 98102, USA; Department of Pathology and 
      Clinical Medicine, Mayo Clinic, Rochester, MN 55905, USA.
FAU - Bartemes, Kathleen R
AU  - Bartemes KR
AD  - Department of Otolaryngology-Head and Neck Surgery, Mayo Clinic, Rochester, MN 
      55905, USA.
FAU - Chatzopoulos, Kyriakos
AU  - Chatzopoulos K
AD  - Department of Pathology and Laboratory Medicine, Mayo Clinic, Rochester, MN 
      55905, USA.
FAU - Price, Daniel L
AU  - Price DL
AD  - Department of Otolaryngology-Head and Neck Surgery, Mayo Clinic, Rochester, MN 
      55905, USA.
FAU - Janus, Jeffrey R
AU  - Janus JR
AD  - Department of Otolaryngology-Head and Neck Surgery, Mayo Clinic, Rochester, MN 
      55905, USA.
FAU - Kasperbauer, Jan L
AU  - Kasperbauer JL
AD  - Department of Otolaryngology-Head and Neck Surgery, Mayo Clinic, Rochester, MN 
      55905, USA.
FAU - Price, Katharine A
AU  - Price KA
AD  - Department of Medical Oncology, Mayo Clinic, Rochester, MN 55905, USA.
FAU - Chintakuntlawar, Ashish V
AU  - Chintakuntlawar AV
AD  - Department of Medical Oncology, Mayo Clinic, Rochester, MN 55905, USA.
FAU - Neben-Wittich, Michelle A
AU  - Neben-Wittich MA
AD  - Department of Radiation Oncology, Mayo Clinic, Rochester, MN 55905, USA.
FAU - Foote, Robert L
AU  - Foote RL
AD  - Department of Radiation Oncology, Mayo Clinic, Rochester, MN 55905, USA.
FAU - Garcia, Joaquin J
AU  - Garcia JJ
AD  - Department of Pathology and Laboratory Medicine, Mayo Clinic, Rochester, MN 
      55905, USA.
LA  - eng
PT  - Journal Article
DEP - 20200723
PL  - England
TA  - Oral Oncol
JT  - Oral oncology
JID - 9709118
SB  - IM
MH  - Adult
MH  - Age Factors
MH  - Aged
MH  - Aged, 80 and over
MH  - Alphapapillomavirus/*immunology
MH  - Case-Control Studies
MH  - Disease Progression
MH  - Female
MH  - Gene Rearrangement, beta-Chain T-Cell Antigen Receptor/immunology
MH  - Human papillomavirus 16/immunology
MH  - Humans
MH  - Kaplan-Meier Estimate
MH  - Lymph Nodes/pathology
MH  - Lymphatic Metastasis
MH  - Lymphocyte Count
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Staging
MH  - Oropharyngeal Neoplasms/*immunology/mortality/pathology/virology
MH  - Progression-Free Survival
MH  - Sex Factors
MH  - Squamous Cell Carcinoma of Head and Neck/*immunology/mortality/pathology/virology
MH  - T-Lymphocytes/*cytology
MH  - Tumor Burden
MH  - Tumor Microenvironment/*immunology
OTO - NOTNLM
OT  - ACE-27
OT  - Comorbidities
OT  - HPV
OT  - Human papillomavirus
OT  - Immune
OT  - Immunoseq
OT  - Oropharyngeal
OT  - Oropharynx
OT  - Squamous cell carcinoma
OT  - T cell clonality
OT  - T cell repertoire
OT  - Tumor microenvironment
EDAT- 2020/07/28 06:00
MHDA- 2021/09/14 06:00
CRDT- 2020/07/27 06:00
PHST- 2020/06/02 00:00 [received]
PHST- 2020/06/22 00:00 [revised]
PHST- 2020/07/01 00:00 [accepted]
PHST- 2020/07/28 06:00 [pubmed]
PHST- 2021/09/14 06:00 [medline]
PHST- 2020/07/27 06:00 [entrez]
AID - S1368-8375(20)30330-4 [pii]
AID - 10.1016/j.oraloncology.2020.104894 [doi]
PST - ppublish
SO  - Oral Oncol. 2020 Dec;111:104894. doi: 10.1016/j.oraloncology.2020.104894. Epub 
      2020 Jul 23.