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

Author(s):Show less -

Sales de Sa, Raisa ^[1] ; Miranda Galvis, Marisol ^{[1, 2]} ; Mariz, Bruno Augusto Linhares Almeida ^[1] ; Leite, Amanda Almeida ^[1] ; Schultz, Luciana ^[3] ; Almeida, Oslei Paes ^[1] ; Santos-Silva, Alan Roger ^[1] ; Pinto, Clovis Antonio Lopes ^[4] ; Vargas, Pablo Agustin ^[1] ; Gollob, Kenneth John ^{[5, 6]} ; Kowalski, Luiz Paulo ^{[7, 8]}

Affiliation

^[1] Univ Estadual Campinas, Piracicaba Dent Sch, Dept Oral Diag, Piracicaba - Brazil

^[2] Augusta Univ, Dept Oral Biol & Diagnost Sci, Dent Coll Georgia, Augusta, GA - USA

^[3] Inst Anat Patol IAP, Dept Anat Pathol, Santa Barbara Doeste - Brazil

^[4] AC Camargo Canc Ctr, Dept Anat Pathol, Sao Paulo - Brazil

^[5] AC Camargo Canc Ctr, Int Res Ctr, Sao Paulo - Brazil

^[6] AC Camargo Canc Ctr, Natl Inst Sci & Technol Oncogen & Therapeut Innov, Sao Paulo - Brazil

^[7] AC Camargo Canc Ctr, Dept Head & Neck Surg & Otorhinolaryngol, Sao Paulo - Brazil

^[8] Univ Sao Paulo, Med Sch, Head & Neck Surg Dept, Sao Paulo - Brazil

• Document type: Journal article
• Source: FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY; v. 8, FEB 18 2021.
• Web of Science Citations: 0

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. (AU)

• FAPESP's process: 18/24715-2 - FGF-2, FGFR-1, PI3K, Akt and COX-2 expression in Oral Leucoplakia, primary and metastatic Oral Squamous Cell Carcinoma
• Grantee: Bruno Augusto Linhares Almeida Mariz
• Support Opportunities: Scholarships in Brazil - Doctorate