Head and neck squamous cell carcinoma is a heterogeneous cancer with varying prognoses depending on anatomical location and characteristics, and advanced cancers have a poor prognosis. This study aimed to examine changes in the tumor microenvironment and systemic immune system before and after combination therapy with immune checkpoint inhibitors, the standard first-line treatment for head and neck cancer. The rationale for this research and development project is as follows: 1. While immune checkpoint inhibitors have improved survival rates for head and neck cancer patients, they are only effective in approximately 15% of patients. Because biomarkers predicting treatment response have not yet been clearly identified, targeting target patient populations is challenging. 2. While numerous studies have examined the tumor microenvironment in head and neck cancer, no studies have spatially compared dynamic changes before and after immune checkpoint inhibitor treatment using paired tissue and blood biopsies. Therefore, the specific treatment mechanisms remain unclear. 3. Little is known about how changes in the tumor microenvironment are reflected in the peripheral blood, making noninvasive treatment response monitoring difficult. 4. Immune checkpoint inhibitor treatment is known to enhance the efficacy of subsequent taxane-based chemotherapy, but the mechanism remains unknown. Therefore, we aim to explore biomarkers that predict treatment response to combination therapy with immune checkpoint inhibitors and cytotoxic chemotherapy in patients with advanced/metastatic head and neck cancer and develop personalized treatment strategies.