Core Viewpoint - Immune checkpoint blockade (ICB) therapy has shown promise in improving clinical outcomes for some head and neck squamous cell carcinoma (HNSCC) patients, but the mechanisms regulating treatment response remain poorly understood [3][6]. Group 1: Role of Gut Microbiome - Increasing research emphasizes the significant role of the gut microbiome in determining the effectiveness of immunotherapy, with specific gut bacteria shown to enhance anti-tumor immunity and T cell proliferation in cancer patients [3]. - Intratumoral bacteria have been identified as immunosuppressive and promote resistance to ICB therapy in HNSCC [4]. Group 2: Research Findings - A study analyzing samples from the CIAO clinical trial found that only the total abundance of intratumoral bacteria could predict patient response to ICB therapy, a conclusion validated across multiple independent cohorts [6]. - High abundance of intratumoral bacteria correlates with an immunosuppressive tumor microenvironment characterized by neutrophil accumulation and reduced T cells and other adaptive immune cells [6]. - Experimental manipulation of intratumoral bacterial abundance in a mouse model of HNSCC replicated the immunological associations observed in clinical trial participants [6]. Group 3: Implications for Immunotherapy - The findings indicate that high levels of intratumoral bacteria are a key inhibitory factor for anti-tumor immunity and contribute to resistance against immunotherapy [7].

Core Viewpoint - Immune checkpoint inhibitors (ICIs) have shown significant breakthroughs in cancer treatment, but only about 20% of patients benefit long-term, necessitating exploration of resistance mechanisms and ways to enhance clinical benefits [2][3]. Group 1: Role of Gut Microbiome - The gut microbiome plays a crucial role in the effectiveness of ICIs, with ongoing clinical trials combining fecal microbiota transplantation with ICIs showing promising results [2][3]. - Research indicates that the intratumoral microbiome is associated with cancer progression, prognosis, and treatment response, highlighting its potential in enhancing immunotherapy effects [2][3]. Group 2: Recent Research Findings - A recent study published in Cell Reports Medicine identified and validated intratumoral bacteria that can synergize with anti-PD-1 therapy, inhibiting tumor growth and enhancing anti-tumor immunity [3][6]. - The study utilized bioinformatics to extract intratumoral microbiome information from RNA sequencing data of clinical cohorts treated with ICIs, establishing correlations between specific microbial modules and patient responses [5][6]. Group 3: Key Discoveries - The study's core findings emphasize the association between the intratumoral microbiome and immune therapy responses, with specific microbial features linked to tumor microenvironment characteristics [7][9]. - The identified intratumoral bacteria, including Burkholderia cepacia, Priestia megaterium, and Corynebacterium kroppenstedtii, were shown to enhance anti-tumor immunity in mouse models when injected intratumorally [6][7].