Smith Joshua D, Gensterblum-Miller Elizabeth, Forner David W A, Yalamanchi Pratyusha, Buchakjian Marisa R, Chinn Steven B, Shuman Andrew G, Casper Keith A, Malloy Kelly M, Stucken Chaz L, Mclean Scott A, Mierzwa Michelle L, Shah Jennifer, Swiecicki Paul L, Worden Francis P, Prince Mark E P, Spector Matthew E, Brenner J Chad, Heft Neal Molly E
Department of Otolaryngology-Head and Neck Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
Department of Otolaryngology-Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan, USA.
Otolaryngol Head Neck Surg. 2025 May 5. doi: 10.1002/ohn.1291.
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.
Retrospective cohort study.
Tertiary care hospital.
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.
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%).
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.
我们评估了作为肿瘤缺氧标志物的肿瘤碳酸酐酶IX（CAIX）染色与一组接受生物选择方法进行确定性治疗的晚期喉鳞状细胞癌患者中CD8 T细胞浸润之间的相关性。
回顾性队列研究。
三级护理医院。
纳入在生物选择模式下接受治疗的III至IV期喉鳞状细胞癌患者。进行了CD8 T细胞和CAIX的免疫组织化学检测。使用非参数检验和Kaplan-Meier生存分析，通过临床病理变量和CD8 T细胞浸润比较肿瘤CAIX状态，并评估CAIX以及CAIX/肿瘤浸润淋巴细胞（TIL）组合类别对生存的作用。
我们的队列包括92例患者（n = 68 [73.9%]为声门上型）。在肿瘤亚部位、分期和诱导化疗反应方面，CAIX染色无差异（所有P > 0.05）。13例（14.1%）肿瘤为CAIX阳性，其CD8 T细胞浸润显著低于CAIX阴性肿瘤（18 [0 - 62]对32 [0 - 399]，P = 0.028）。CAIX/TIL组合类别与反应可能性显著相关（CAIX阴性/TIL[高]反应可能性较小），在反应组中，可预测更高程度的肿瘤缩小（>80%）。
在接受生物选择的晚期喉鳞状细胞癌患者中，CAIX染色与CD8 T细胞浸润减少相关。CAIX/TIL组合类别与诱导反应的可能性和程度相关。CAIX状态以及其他免疫和缺氧组合特征作为诱导反应和生存生物标志物的效用值得进行前瞻性评估。
