TY - JOUR
T1 - Characterization of the tumor immune microenvironment of sinonasal squamous-cell carcinoma
AU - Gu, Jeffrey T.
AU - Claudio, Natalie
AU - Betts, Courtney
AU - Sivagnanam, Shamilene
AU - Geltzeiler, Mathew
AU - Pucci, Ferdinando
N1 - Funding Information:
information Department of Otolaryngology–Head and Neck Surgery, Oregon Health and Science University (to J.T.G. and F.P.); National Institutes of Health (1U01 CA224012, U2C CA233280, R01 CA223150, R01 CA226909, R21 HD099367 to C.B. and S.S. via Dr Lisa M. Coussens); the Knight Cancer Institute; Brenden-Colson Center for Pancreatic Care at OHSU; National Cancer Institute Human Tumor Atlas Network Research Center (U2C CA233280); Prospect Creek Foundation to the OHSU Serial Measurement of Molecular and Architectural Responses to Therapy Program.The authors thank Dr Lisa Coussens for technical assistance with the mIHC analytics platform and troubleshooting support, and Dr Paul Flint for departmental support and assistance.
Publisher Copyright:
© 2021 ARS-AAOA, LLC
PY - 2022/1
Y1 - 2022/1
N2 - Background: Treatment and prognosis of sinonasal squamous-cell carcinoma (SNSCC) have not significantly improved despite improvements in radical therapy. Characterization of the tumor immune microenvironment (TiME) may identify patient subgroups associated with disease recurrence, and provide new biomarkers for improved patient stratification and treatment. Methods: The TiME was quantitatively evaluated by multiplex immunohistochemistry (mIHC) in archived tissue sections from 38 patients with SNSCC, and were assessed for differences between recurrent (n = 20) and nonrecurrent (n = 18) groups. Hierarchical clustering analyses were performed to identify phenotypic TiME subgroups within the cohort and were used to compare survival outcomes. Results: Our mIHC analysis revealed increased T-cell populations and decreased myeloid-cell populations in SNSCC patients without recurrent disease, as compared with patients with recurrent disease. Within T-cell subsets, there was a significantly higher percentage of granzyme B+, T-bet+, Eomes+ T cells, as well as higher proliferation of CD8+ T cells within the nonrecurrent group relative to the recurrent group. Furthermore, immune-cell complexity profiles of SNSCC revealed hyper– and hypo–T-cell–inflamed, myeloid-inflamed, B-cell–inflamed, and broadly hypoinflamed subtypes not previously identified by gene expression analyses. Our study revealed that presence of either hyper– or hypo–T-cell–inflamed TiME subtypes were associated with increased survival outcomes as compared with broadly hypoinflamed TiME subtypes (p = 0.035 and 0.0376, respectively). Conclusions: The TiME of SNSCC reveals distinct subtypes, which may correlate with recurrence and survival outcomes.
AB - Background: Treatment and prognosis of sinonasal squamous-cell carcinoma (SNSCC) have not significantly improved despite improvements in radical therapy. Characterization of the tumor immune microenvironment (TiME) may identify patient subgroups associated with disease recurrence, and provide new biomarkers for improved patient stratification and treatment. Methods: The TiME was quantitatively evaluated by multiplex immunohistochemistry (mIHC) in archived tissue sections from 38 patients with SNSCC, and were assessed for differences between recurrent (n = 20) and nonrecurrent (n = 18) groups. Hierarchical clustering analyses were performed to identify phenotypic TiME subgroups within the cohort and were used to compare survival outcomes. Results: Our mIHC analysis revealed increased T-cell populations and decreased myeloid-cell populations in SNSCC patients without recurrent disease, as compared with patients with recurrent disease. Within T-cell subsets, there was a significantly higher percentage of granzyme B+, T-bet+, Eomes+ T cells, as well as higher proliferation of CD8+ T cells within the nonrecurrent group relative to the recurrent group. Furthermore, immune-cell complexity profiles of SNSCC revealed hyper– and hypo–T-cell–inflamed, myeloid-inflamed, B-cell–inflamed, and broadly hypoinflamed subtypes not previously identified by gene expression analyses. Our study revealed that presence of either hyper– or hypo–T-cell–inflamed TiME subtypes were associated with increased survival outcomes as compared with broadly hypoinflamed TiME subtypes (p = 0.035 and 0.0376, respectively). Conclusions: The TiME of SNSCC reveals distinct subtypes, which may correlate with recurrence and survival outcomes.
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U2 - 10.1002/alr.22867
DO - 10.1002/alr.22867
M3 - Article
C2 - 34510766
AN - SCOPUS:85114670327
VL - 12
SP - 39
EP - 50
JO - International Forum of Allergy and Rhinology
JF - International Forum of Allergy and Rhinology
SN - 2042-6976
IS - 1
ER -