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Tumor Hypoxia and CD8+ T-Cell Infiltration in Patients With Advanced Laryngeal Cancer
Joshua D Smith1, Elizabeth Gensterblum-Miller2, David W A Forner2
1Department of Otolaryngology-Head and Neck Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
Objective:
We assessed correlations between tumor carbonic anhydrase IX (CAIX) staining, as a marker of tumor hypoxia, and CD8+ T-cell infiltration in a cohort of patients with advanced laryngeal squamous cell carcinoma undergoing a bioselection approach for definitive treatment.
Study Design:
Retrospective cohort study.
Setting:
Tertiary care hospital.
Methods:
Patients with stage III to IV laryngeal squamous cell carcinoma treated under a bioselection paradigm were included. Immunohistochemistry for CD8+ T-cells and CAIX was performed. Nonparametric tests and Kaplan-Meier survival analyses were used to compare tumor CAIX status by clinicopathologic variables and CD8+ T-cell infiltration and to evaluate the role of CAIX and combination CAIX/tumor infiltrating lymphocytes (TIL) category on survival.
Results:
Our cohort included 92 patients (n = 68 [73.9%] supraglottic). No difference in CAIX staining was seen by tumor subsite, stage, and response to induction chemotherapy (all P > .05). Thirteen (14.1%) tumors were CAIX-positive and showed significantly lower CD8+ T-cell infiltration than CAIX-negative tumors (18 [0-62] vs 32 [0-399], P = .028). Combination CAIX/TIL category was significantly associated with the likelihood of response (CAIX-/TIL[high] were less likely to respond) and in the group of responders, was predictive of a higher degree of tumor shrinkage (>80%).
Conclusion:
CAIX staining correlates with reduced CD8+ T-cell infiltration in patients with advanced laryngeal squamous cell carcinoma undergoing bioselection. The combination CAIX/TIL category is associated with the likelihood and degree of response to induction. The utility of CAIX status and other combination immune and hypoxia signatures as a biomarker of induction response and survival merits prospective evaluation.
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