Increased Tumor Immune Microenvironment CD3+ and CD20+ Lymphocytes Predict a Better Prognosis in Oral Tongue Squamous Cell Carcinoma

Raísa Sales de Sá; Marisol Miranda Galvis; Bruno Augusto Linhares Almeida Mariz; Amanda Almeida Leite; Luciana Schultz; Oslei Paes Almeida; Alan Roger Santos-Silva; Clovis Antonio Lopes Pinto; Pablo Agustin Vargas; Kenneth John Gollob; Luiz Paulo Kowalski

doi:10.3389/fcell.2020.622161

Increased Tumor Immune Microenvironment CD3+ and CD20+ Lymphocytes Predict a Better Prognosis in Oral Tongue Squamous Cell Carcinoma

Front Cell Dev Biol. 2021 Feb 18:8:622161. doi: 10.3389/fcell.2020.622161. eCollection 2020.

Affiliations

¹ Department of Oral Diagnosis, Piracicaba Dental School, University of Campinas, Piracicaba, Brazil.
² Department of Oral Biology and Diagnostic Sciences, Dental College of Georgia, Augusta University, Augusta, GA, United States.
³ Department of Anatomic Pathology, Instituto de Anatomia Patologica-IAP, Santa Barbara d'Oeste, Brazil.
⁴ Department of Anatomic Pathology, A. C. Camargo Cancer Center, São Paulo, Brazil.
⁵ International Research Center, A. C. Camargo Cancer Center, São Paulo, Brazil.
⁶ National Institute for Science and Technology in Oncogenomics and Therapeutic Innovation, A.C. Camargo Cancer Center, São Paulo, Brazil.
⁷ Department of Head and Neck Surgery and Otorhinolaryngology, A. C. Camargo Cancer Center, São Paulo, Brazil.
⁸ Head and Neck Surgery Department, Medical School, University of São Paulo, São Paulo, Brazil.

Abstract

Background: Oral tongue squamous cell carcinoma (OTSCC) causes over 350,000 cases annually and particularly impacts populations in developing countries. Smoking and alcohol consumption are major risk factors. Determining the role of the tumor immune microenvironment (TIME) in OTSCC outcomes can elucidate immune mechanisms behind disease progression, and can potentially identify prognostic biomarkers. Methods: We performed a retrospective study of 48 OTSCC surgical specimens from patients with tobacco and alcohol exposures. A panel of immunoregulatory cell subpopulations including T (CD3, CD4, CD8) and B (CD20) lymphocytes, dendritic cells (CD1a, CD83), macrophages (CD68), and immune checkpoint molecules programmed cell death protein 1 (PD-1) and ligand 1 (PD-L1) were analyzed using immunohistochemistry. The levels of immune effector cell subpopulations and markers were analyzed in relation to overall survival. Results: Pathological characteristics of the tumor microenvironment included inflammatory infiltrates (83.3%), desmoplasia (41.6%), and perineural invasion (50.0%). The TIME contained high levels of T cells (CD3+, CD4+, and CD8+) and B cells (CD20+), as well as immature (CD1a) and mature (CD83) dendritic cells, PD-1, and PD-L1. Higher numbers of TIME infiltrating CD3+ T cells and CD20+ B cells were predictive of better survival, while higher levels of CD83+ mature dendritic cells predicted better survival. CD3+ T cells were identified as an independent prognostic marker for OTSCC. Lastly, CD3+ T cells were strongly correlated with the number of CD8+ cells and PD-L1 expression. Conclusion: Our findings provide evidence that the TIME profile of OTSSC impacted prognosis. The high expression of CD3+ T cells and B cells are predictive of better overall survival and indicative of an immunologically active, inflammatory TIME in patients with better survival. The number of CD3+ T cells was an independent prognostic marker.

Keywords: CD20 B cells+; CD3; immune microenvironment; tongue squamous cell carcinoma (TSCC); tumor-infiltrating lymphocytes.