Raísa Sales de Sá1, Marisol Miranda Galvis1,2, Bruno Augusto Linhares Almeida Mariz1, Amanda Almeida Leite1, Luciana Schultz3, Oslei Paes Almeida1, Alan Roger Santos-Silva1, Clovis Antonio Lopes Pinto4, Pablo Agustin Vargas1, Kenneth John Gollob5,6, Luiz Paulo Kowalski7,8. 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.
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.
Authors: Alhadi Almangush; Antti A Mäkitie; Asterios Triantafyllou; Remco de Bree; Primož Strojan; Alessandra Rinaldo; Juan C Hernandez-Prera; Carlos Suárez; Luiz P Kowalski; Alfio Ferlito; Ilmo Leivo Journal: Oral Oncol Date: 2020-05-20 Impact factor: 5.337
Authors: Benjamin A Kansy; Fernando Concha-Benavente; Raghvendra M Srivastava; Hyun-Bae Jie; Gulidanna Shayan; Yu Lei; Jessica Moskovitz; Jennifer Moy; Jing Li; Sven Brandau; Stephan Lang; Nicole C Schmitt; Gordon J Freeman; William E Gooding; David A Clump; Robert L Ferris Journal: Cancer Res Date: 2017-09-13 Impact factor: 12.701
Authors: Wattawan Wongpattaraworakul; Katherine N Gibson-Corley; Allen Choi; Marisa R Buchakjian; Emily A Lanzel; Anand Rajan Kd; Andrean L Simons Journal: Front Oncol Date: 2022-07-25 Impact factor: 5.738