Tumor Hypoxia Correlates With Reduced CD8+ TILs in Patients With Advanced Laryngeal Cancer Undergoing Bioselection

Sunday, September 29, 2024

9:48 AM – 9:54 AM EDT

Location: MBCC, 208

Disclosure(s):

Elizabeth Gensterblum-Miller, PhD:

faculty for this accredited education activity has no relationship(s) with ineligible companies to disclose.

Chad J. Brenner, PhD:

faculty for this accredited education activity has no relationship(s) with ineligible companies to disclose.

Matthew E. Spector, MD:

faculty for this accredited education activity has no relationship(s) with ineligible companies to disclose.

Molly E. Heft Neal, MD:

faculty for this accredited education activity has no relationship(s) with ineligible companies to disclose.

Introduction: Tumor CD8+ T-cell infiltration (TILs) is an independent predictor of survival outcomes in patients with advanced laryngeal squamous cell carcinoma (LSCC) undergoing a bioselection approach for definitive treatment selection. The mechanistic interplay between tumor hypoxia and CD8+ TIL content in these patients is unknown. Here, we assessed correlations between tumor carbonic anhydrase IX (CAIX) staining, as a marker of tumor hypoxia, and CD8+ TILs in a large cohort of such patients.

Methods: Patients with advanced LSCC treated with bioselection and available pre-treatment biopsy tissue for TMA construction were included. IHC for CD8+ TILs (1:40 Nova Castra VP-C320) and CAIX (#CAIX-L-CE Leica) was performed. Student’s t-test was used to compare CD8+ TIL counts between CAIX-positive and CAIX-negative tumors. Statistical significance was defined as p ≤ 0.05.

Results: Our cohort consisted of 92 patients with advanced LSCC, including 68 (73.9%) supraglottic, 23 (25%) glottic, and 1 (1.1%) subglottic subsites. Twenty (21.7%) were Stage III and 72 (78.3%) were Stage IV. Most patients (n = 77, 83.7%) were responders to induction chemotherapy and went on to receive definitive chemoradiotherapy. No difference in CAIX staining was seen by tumor subsite, stage, and response to induction chemotherapy (all p > 0.05) Thirteen (14.1%) tumors were CAIX-positive and 79 (85.9%) were CIAX-negative. CAIX-positive tumors showed significantly lower CD8+ TIL content than CAIX-negative tumors (18 [0-62] vs 32 [0-399], p = 0.028).

Conclusions: CAIX staining, as a marker of tumor hypoxia, correlates with reduced CD8+ TIL content in patients with advanced LSCC undergoing a bioselection approach for definitive treatment selection. Future studies investigating the mechanistic relationship between hypoxic phenotypes and tumor immune evasion in this population are warranted. Further, utility of CAIX status as a biomarker of induction response and survival in these patients is justified in larger cohorts.

Presenting Author(s)

JS

Joshua D. Smith, MD

Resident
University of Pittsburgh Otolaryngology
Ann Arbor, MI, United States

Disclosure information not submitted.

Co-Author(s)

EG

Elizabeth Gensterblum-Miller, PhD

Postdoctoral fellow
University of Michigan
Ann Arbor, MI, United States

Disclosure(s):
faculty for this accredited education activity has no relationship(s) with ineligible companies to disclose.
Chad J. Brenner, PhD

Associate Professor
University of Michigan
Ann Arbor, MI, United States

Disclosure(s):
faculty for this accredited education activity has no relationship(s) with ineligible companies to disclose.
MS

Matthew E. Spector, MD

Professor
Department of Otolaryngology, University of Pittsburgh Medical Center
Pittsburgh, PA, United States

Disclosure(s):
faculty for this accredited education activity has no relationship(s) with ineligible companies to disclose.

Senior Author(s)

Molly E. Heft Neal, MD

Assistant Professor
University of Michigan
Ann Arbor, MI, United States

Disclosure(s):
faculty for this accredited education activity has no relationship(s) with ineligible companies to disclose.