Doescher Johannes, von Witzleben Adrian, Boukas Konstantinos, Weissinger Stephanie E, Thomas Gareth J, Laban Simon, Thomas Jaya, Hoffmann Thomas K, Ottensmeier Christian H
Translational Immunology Group, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, United Kingdom.
Department of Otorhinolaryngology, Head and Neck Surgery, Ulm University Medical Center, Ulm, Germany.
Front Oncol. 2022 Apr 1;12:862694. doi: 10.3389/fonc.2022.862694. eCollection 2022.
Chemoradiotherapy (CRT) is a standard treatment for advanced head and neck squamous cell carcinoma (HNSCC). Unfortunately, not all patients respond to this therapy and require further treatment, either salvage surgery or palliative therapy. The addition of immunotherapy to CRT is currently being investigated and early results describe a mixed response. Therefore, it is important to understand the impact of CRT on the tumor microenvironment (TME) to be able to interpret the results of the clinical trials. Paired biopsies from 30 HNSCC patients were collected before and three months after completion of primary CRT and interrogated for the expression of 1392 immune- and cancer-related genes. There was a relevant difference in the number of differentially expressed genes between the total cohort and patients with residual disease. Genes involved in T cell activation showed significantly reduced expression in these tumors after therapy. Furthermore, gene enrichment for several T cell subsets confirmed this observation. The analysis of tissue resident memory T cells (T) did not show a clear association with impaired response to therapy. CRT seems to lead to a loss of T cells in patients with incomplete response that needs to be reversed. It is not clear whether the addition of anti-PD-1 antibodies alone to CRT can prevent treatment failure, as no upregulation of the targets was measurable in the TME.
放化疗（CRT）是晚期头颈部鳞状细胞癌（HNSCC）的标准治疗方法。不幸的是，并非所有患者都对这种治疗有反应，需要进一步治疗，要么是挽救性手术，要么是姑息治疗。目前正在研究在CRT中加入免疫疗法，早期结果显示反应不一。因此，了解CRT对肿瘤微环境（TME）的影响对于解读临床试验结果很重要。收集了30例HNSCC患者在初次CRT完成前和完成后三个月的配对活检样本，并检测了1392个免疫和癌症相关基因的表达。在整个队列和有残留疾病的患者之间，差异表达基因的数量存在显著差异。参与T细胞活化的基因在治疗后这些肿瘤中的表达显著降低。此外，对几个T细胞亚群的基因富集证实了这一观察结果。对组织驻留记忆T细胞（T）的分析未显示与治疗反应受损有明显关联。CRT似乎导致反应不完全的患者T细胞丢失，这需要扭转。目前尚不清楚仅在CRT中加入抗PD-1抗体是否能预防治疗失败，因为在TME中未检测到靶点的上调。
