Tumor‐Infiltrating Lymphocytes in Patients With Advanced Laryngeal Cancer Undergoing Bioselection

Abstract

Objective Bioselection to assess tumor response after induction chemotherapy has been introduced as an alternative treatment strategy to total laryngectomy for patients with advanced larynx squamous cell carcinoma (LSCC). Tumor-infiltrating lymphocytes (TILs) have proven to serve as prognostic biomarkers in head and neck cancer but have not been evaluated as a way to select patients for treatment paradigms. The aim of this study is to evaluate the role of pretreatment TILs in patients with advanced LSCC undergoing the bioselection paradigm. Study Design Retrospective study. Setting Tertiary care hospital. Methods Patients with advanced LSCC treated with bioselection and available tissue were included (N = 76). Patients were stratified into CD8-low and CD8-high cohorts by using the median TIL count. Kaplan-Meier survival analysis and multivariate cox regression were performed with SPSS version 26 (IBM). Results After controlling for tobacco use, tumor site, and stage, a high CD8 TIL count was an independent predictor of improved 5-year disease-specific survival (hazard ratio, 0.17 [95% CI, 0.03-0.84]; P = .03). CD8 TIL counts did not predict response to induction chemotherapy; however, subgroup analysis of patients treated with chemoradiation therapy revealed that CD8 TIL count was significantly associated with degree of response ( P = .012). Conclusion These findings support prior data published by our group showing that TILs are predictive of disease-specific survival in patients with head and neck cancer. CD8 TIL counts were significantly associated with degree of clinical response after induction chemotherapy. These results suggest that pretreatment assessment of tumor-infiltrating CD8 cells could be useful in selecting patients.

A multicenter protocol to assess the prognostic significance of the tumor microenvironment in patients with squamous cell carcinoma of the larynx

“…According to the score proposed by Salgado et al, 8 52% (97) tumors had moderate score and 35% (66) low score, only 9% (17) presented an intense score. Ninety-six percent cases presented TILs, which were absent in only six occasions (4%).…”

“…5 The importance of TILs as bioselectors for risk stratification of patients into treatment groups was confirmed by a meta-analysis by Brosetto et al 16 The role of pretreatment TILs in patients with advanced LSCC undergoing bioselection was evaluated by Heft Neal et al In this work, CD8+ TILs count was an independent predictor of improved 5-year DSS and was significantly associated with the degree of clinical response after induction ChT, supporting the thesis that pre-treatment assessment of CD8+ TILs could be a strong selector for patients. 17 Salvage laryngectomy is the gold standard for recurrent LSCC after organ preservation with RT or ChT; a cohort of 183 patients undergoing salvage TL was evaluated by Hoesli et al who found that elevated levels of CD8 and CD4 positive TILs were associated with improved disease-specific survival (DSS) and disease-free survival (DFS), and they noted the hypothesis that elevated percentage of CD8 and possibly CD4 positive TILs may represent a positive prognostic factor for LSCC. 18 Also, the findings of the work from Mann et al confirmed the prognostic role of TILs in recurrent LSCC and the need to identify predictive models to lead to personalized treatment paradigms.…”