Mario Sanchez-Canteli1, Rocio Granda-Díaz1,2, Nagore Del Rio-Ibisate1,2, Eva Allonca1,2, Fernando López-Alvarez1,2, Jackeline Agorreta2,3, Irati Garmendia2,3, Luis M Montuenga2,3, Juana M García-Pedrero4,5,6, Juan P Rodrigo7,8,9. 1. Department of Otolaryngology, Hospital Universitario Central de Asturias and Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Instituto Universitario de Oncología del Principado de Asturias, University of Oviedo, 33011, Oviedo, Spain. 2. Ciber de Cáncer, CIBERONC, 28029, Madrid, Spain. 3. Program in Solid Tumors, Center for Applied Medical Research (CIMA), Department of Pathology, Anatomy and Physiology, University of Navarra and Navarra's Health Research Institute (IDISNA), 31008, Pamplona, Spain. 4. Department of Otolaryngology, Hospital Universitario Central de Asturias and Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Instituto Universitario de Oncología del Principado de Asturias, University of Oviedo, 33011, Oviedo, Spain. juanagp.finba@gmail.com. 5. Ciber de Cáncer, CIBERONC, 28029, Madrid, Spain. juanagp.finba@gmail.com. 6. Lab ORL, Edificio FINBA, Hospital Universitario Central de Asturias, Avda Roma s/n 33011, Oviedo, Spain. juanagp.finba@gmail.com. 7. Department of Otolaryngology, Hospital Universitario Central de Asturias and Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Instituto Universitario de Oncología del Principado de Asturias, University of Oviedo, 33011, Oviedo, Spain. jprodrigo@uniovi.es. 8. Ciber de Cáncer, CIBERONC, 28029, Madrid, Spain. jprodrigo@uniovi.es. 9. Lab ORL, Edificio FINBA, Hospital Universitario Central de Asturias, Avda Roma s/n 33011, Oviedo, Spain. jprodrigo@uniovi.es.
Abstract
INTRODUCTION: The importance of immune tumor microenvironment in the prognosis of patients with head and neck squamous carcinomas (HNSCC) is increasingly recognized. We analyzed the prognostic relevance of PD-L1 and PD-1 expressions in relation to the infiltration by CD8+ and FOXP3+ tumor-infiltrating lymphocytes (TILs). METHODS: Samples from 372 surgically treated HPV-negative HNSCC patients were evaluated by immunohistochemistry for PD-L1 expression [both tumor proportion score (TPS) and combined proportion score (CPS)], PD-1 expression in immune cells, and density of infiltrating CD8+ and FOXP3+ TILs. PD-L1 expression and CD8+ TIL density were combined to establish the type of tumor microenvironment. RESULTS: 29.5% cases exhibited PD-L1 TPS positivity (≥ 1%), whereas PD-L1 CPS positivity (≥ 1%) was observed in 40% cases. 47.5% cases showed positive PD-1 expression (≥ 1%). PD-L1 and PD-1 positivity correlated with a high density of both CD8+ and FOXP3+ TILs. In univariate analysis, PD-L1 TPS positivity (P = 0.026), PD-L1 CPS positivity (P = 0.004), high density of CD8+ TIL (P = 0.001), and high density of FOXP3+ TIL (P = 0.004) were associated with a better disease-specific survival (DSS). However, in multivariate analysis, only high density of CD8+ TIL was associated with a better DSS (P = 0.002). The type of tumor microenvironment correlated with DSS (P = .008), with the better DSS observed in cases with type I (PD-L1 CPS positivity and high density of CD8+ TIL). CONCLUSIONS: High infiltration by CD8+ TIL is associated with better survival outcomes. Positive PD-L1 expression correlates with a high infiltration by TILs, explaining its association with better prognosis.
INTRODUCTION: The importance of immune tumor microenvironment in the prognosis of patients with head and neck squamous carcinomas (HNSCC) is increasingly recognized. We analyzed the prognostic relevance of PD-L1 and PD-1 expressions in relation to the infiltration by CD8+ and FOXP3+ tumor-infiltrating lymphocytes (TILs). METHODS: Samples from 372 surgically treated HPV-negative HNSCCpatients were evaluated by immunohistochemistry for PD-L1 expression [both tumor proportion score (TPS) and combined proportion score (CPS)], PD-1 expression in immune cells, and density of infiltrating CD8+ and FOXP3+ TILs. PD-L1 expression and CD8+ TIL density were combined to establish the type of tumor microenvironment. RESULTS: 29.5% cases exhibited PD-L1 TPS positivity (≥ 1%), whereas PD-L1CPS positivity (≥ 1%) was observed in 40% cases. 47.5% cases showed positive PD-1 expression (≥ 1%). PD-L1 and PD-1 positivity correlated with a high density of both CD8+ and FOXP3+ TILs. In univariate analysis, PD-L1 TPS positivity (P = 0.026), PD-L1CPS positivity (P = 0.004), high density of CD8+ TIL (P = 0.001), and high density of FOXP3+ TIL (P = 0.004) were associated with a better disease-specific survival (DSS). However, in multivariate analysis, only high density of CD8+ TIL was associated with a better DSS (P = 0.002). The type of tumor microenvironment correlated with DSS (P = .008), with the better DSS observed in cases with type I (PD-L1CPS positivity and high density of CD8+ TIL). CONCLUSIONS: High infiltration by CD8+ TIL is associated with better survival outcomes. Positive PD-L1 expression correlates with a high infiltration by TILs, explaining its association with better prognosis.
Entities:
Keywords:
Head and neck cancer; PD-L1; Prognosis; Tumor-infiltrating lymphocytes
Authors: Mario Sánchez-Canteli; Luis Juesas; Esther Redin; Alfonso Calvo; Fernando López; Aurora Astudillo; Luis M Montuenga; Juana M García-Pedrero; Juan P Rodrigo Journal: Cancers (Basel) Date: 2021-04-25 Impact factor: 6.639
Authors: Juan P Rodrigo; Mario Sánchez-Canteli; Fernando López; Gregory T Wolf; Juan C Hernández-Prera; Michelle D Williams; Stefan M Willems; Alessandro Franchi; Andrés Coca-Pelaz; Alfio Ferlito Journal: Biomedicines Date: 2021-04-28
Authors: Bin Xu; Abeer M Salama; Cristina Valero; Avery Yuan; Anjanie Khimraj; Maelle Saliba; Daniella K Zanoni; Ian Ganly; Ronald Ghossein; Snehal G Patel; Nora Katabi Journal: Pathol Res Pract Date: 2021-05-10 Impact factor: 3.309
Authors: Saeed Asiry; Gina Kim; Panagiota S Filippou; Luis Rivera Sanchez; David Entenberg; Douglas K Marks; Maja H Oktay; George S Karagiannis Journal: Front Immunol Date: 2021-04-13 Impact factor: 7.561