TY - JOUR
T1 - T cell fraction impacts oncologic outcomes in human papillomavirus associated oropharyngeal squamous cell carcinoma
AU - Van Abel, Kathryn M.
AU - Routman, David M.
AU - Moore, Eric J.
AU - Ma, Daniel J.
AU - Yin, Linda X.
AU - Fields, Paul A.
AU - Schofield, Matt
AU - Bartemes, Kathleen R.
AU - Chatzopoulos, Kyriakos
AU - Price, Daniel L.
AU - Janus, Jeffrey R.
AU - Kasperbauer, Jan L.
AU - Price, Katharine A.
AU - Chintakuntlawar, Ashish V.
AU - Neben-Wittich, Michelle A.
AU - Foote, Robert L.
AU - Garcia, Joaquin J.
N1 - Publisher Copyright:
© 2020 Elsevier Ltd
PY - 2020/12
Y1 - 2020/12
N2 - 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 TCRβ 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.
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 TCRβ 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.
KW - ACE-27
KW - Comorbidities
KW - HPV
KW - Human papillomavirus
KW - Immune
KW - Immunoseq
KW - Oropharyngeal
KW - Oropharynx
KW - Squamous cell carcinoma
KW - T cell clonality
KW - T cell repertoire
KW - Tumor microenvironment
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U2 - 10.1016/j.oraloncology.2020.104894
DO - 10.1016/j.oraloncology.2020.104894
M3 - Article
C2 - 32712575
AN - SCOPUS:85088305495
SN - 1368-8375
VL - 111
JO - Oral Oncology
JF - Oral Oncology
M1 - 104894
ER -