Schmidl Benedikt, Lauterbach Maren, Stögbauer Fabian, Mogler Carolin, Ribbat-Idel Julika, Perner Sven, Wollenberg Barbara
Department of Otolaryngology Head and Neck Surgery, Technical University Munich, 81675 Munich, Germany.
Institute of General and Surgical Pathology, TUM School of Medicine and Health, Technical University of Munich, 81675 Munich, Germany.
Int J Mol Sci. 2025 Apr 15;26(8):3719. doi: 10.3390/ijms26083719.
Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous and malignant disease with a limited number of biomarkers and insufficient targeted therapies. The current therapeutic landscape is challenged by low response rates, underscoring the need for new therapeutic targets. The success of immunotherapy in HNSCC has highlighted the importance of the immune microenvironment, and since metabolic reprogramming, especially altered tryptophan metabolism, is an important aspect in immune evasion, the interplay of the two enzymes IDO1 and IL4I1 was investigated in HNSCC to assess their immunosuppressive roles and potential as prognostic biomarkers. The immunohistochemical expression of IDO1 and IL4I1 was evaluated by an experienced head and neck pathologist in a tissue microarray (TMA) of 402 patients with HNSCC. Clinical and pathological data were retrieved, and the overall survival of the patients was calculated. In this study, IDO1 and IL4I1 were expressed by HNSCC tumor cells in the TMA of 402 patients. The overall survival analysis of the clinical data of the patients revealed that high IL4I1 expression was significantly associated with worse OS ( = 0.0073), while IDO1 expression did not reach statistical significance ( = 0.087). The combination of both markers led to a clinically significant stratification of patients. Especially p16-negative OPSCC with a high IL4I1 expression demonstrated poor survival. Immunologic differences between IDO1 and IL4I1 were detected in a TMA of 403 patients, with IDO1 and IL4I1 being expressed by HNSCC. A low IL4I1 expression in HNSCC led to a significantly better OS in this study, while IDO1 expression did not have a significant effect. Additional studies are necessary to investigate the complex interplay in the metabolic reprogramming of tumor cells.
头颈部鳞状细胞癌（HNSCC）是一种异质性恶性疾病，生物标志物数量有限，靶向治疗不足。当前的治疗格局面临着低反应率的挑战，这凸显了对新治疗靶点的需求。免疫疗法在HNSCC中的成功突出了免疫微环境的重要性，由于代谢重编程，尤其是色氨酸代谢改变，是免疫逃逸的一个重要方面，因此在HNSCC中研究了两种酶IDO1和IL4I1的相互作用，以评估它们的免疫抑制作用和作为预后生物标志物的潜力。由一位经验丰富的头颈病理学家在402例HNSCC患者的组织微阵列（TMA）中评估IDO1和IL4I1的免疫组化表达。检索临床和病理数据，并计算患者的总生存期。在本研究中，402例患者的TMA中HNSCC肿瘤细胞表达了IDO1和IL4I1。对患者临床数据的总生存期分析显示，高IL4I1表达与较差的总生存期显著相关（P = 0.0073），而IDO1表达未达到统计学意义（P = 0.087）。两种标志物的联合导致了患者临床上显著的分层。特别是高IL4I1表达的p16阴性口咽鳞状细胞癌患者生存期较差。在403例HNSCC患者的TMA中检测到IDO1和IL4I1之间的免疫学差异，HNSCC表达IDO1和IL4I1。在本研究中，HNSCC中低IL4I1表达导致总生存期显著更好，而IDO1表达没有显著影响。需要进一步研究来探讨肿瘤细胞代谢重编程中的复杂相互作用。
