Background
tumor, Head and neck squamous cell carcinoma, cancer, chemo-resistance, HNSCC
TUMOR, INFILTRATION, CANCER, DISEASE, CAVITY, METASTATIC MELANOMA
Head and neck squamous cell carcinoma (HNSCC) arising on the mucosal surfaces of the oral cavity, sinonasal cavity, pharynx, and larynx represents the eighth most common cancer worldwide, with an estimated annual incidence and mortality of around 880,000 and 445,000 cases, respectively [The immune microenvironment is a dynamic structure in a complex interaction with an evolving cancer, but is affected by specific oncology treatments, particularly the immune checkpoint inhibitors. Therefore, a differential evolution of the TME between responders and non-responders induced by cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) and PD-1 blockade have been observed in a longitudinal study of metastatic melanoma patients [A differential TME-related gene expression analysis between anti-PD-1/PD-L1 immunotherapy responders and patients with a progressive disease requires the use of breakthrough technologies. Indeed, deep analysis of the main cellular subsets including tumor cells, tumor-associated stromal cells, and tumor-infiltrating immune cells should consider their position, their organization in the TME, their state, function and cellular phenotype, their interaction with neighboring cells, and the changes over time caused by immunotherapy. Among these new technologies, single-cell RNA sequencing (scRNA-seq) offers the highest cellular resolution but requires tissue dissociation resulting in the loss of spatial information. Spatial transcriptomics (ST), named “Method of the Year 2020” by Nature Methods, is another powerful technique. It preserves the spatial context of biological data and allow the visualization of gene expression distributions. It is suitable for small samples but is limited by low cellular resolution [Thus, analysis of biopsy samples of patients undergoing immunotherapy might contribute to a better understanding of resistance process but with inherent limitations. These include the invasive nature of the analysis with uncertainties related to patients compliance issues and importantly, the intra-tumor heterogeneity with disparate levels of immune infiltration leading to underestimation of the tumor genomics landscape. Conversely, liquid biopsy may overcome tumor heterogeneity in addition to being noninvasive, allowing continuous monitoring of circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), exosomes, miRNAs, circulating immune cell, and TCR repertoire [The same would apply to miRNAs, a class of endogenous non-coding RNAs involved in post-transcriptional regulation of gene expression and playing an important role in chemo-resistance of cancer cells [In this single-center prospective study, we propose to combine liquid biopsy, tissue biopsy, and clinical data at key time points during the management of patients undergoing anti-PD-1 immunotherapy for R/M HNSCC. We will compare the evolution of gene expression profile between responders and non-responders, using spatial transcriptomics analysis among other technologies.