Antoine Yanni

Background: The immune landscape in head and neck squamous cell carcinoma (HNSCC) has been widely investigated. However, the crucial role played by the lymph node microenvironment in metastatic and non-metastatic HNSCC remains unknown. This systematic review aims to discuss the immunological crosstalk between the tumor and the nodal microenvironment and to describe the distribution of immune cells in metastatic and non-metastatic lymph nodes. Methods: A systematic review was conducted according to the PRISMA guidelines. PubMed, Scopus, and the Cochrane Library were searched for studies published between 1990 and 2025, with the final search performed in December 2025. Prospective and retrospective studies evaluating immune cell infiltration in metastatic and non-metastatic cervical lymph nodes were included, whereas studies focusing exclusively on non-cellular biomarkers and non-English publications were excluded. The risk of bias was assessed using the Newcastle–Ottawa Scale. The results were synthesized narratively, and no meta-analysis was performed. Results: The screening process identified 608 articles, of which 27 met our predefined inclusion criteria. These studies focused on macrophages, dendritic cells, neutrophils, natural killer cells, T helper cells, cytotoxic T cells, regulatory T cells, B cells, total lymphocytes, and surface markers. This systematic review provides a well-structured analysis of current knowledge on the impact of the innate and adaptive immune systems on the response against cancer cells and the recruitment of immune cells in lymph nodes. The most significant findings highlight the crucial role of antigen presentation in the antitumor response, particularly through the recruitment and activation of dendritic cells and subcapsular sinus macrophages in tumor-draining lymph nodes. It also presents in a fairly comprehensible manner that the density of mature dendritic cells, cytotoxic T cells, and B cells is higher in non-metastatic lymph nodes. Discussion: The lymph node microenvironment is highly enriched with immune cell infiltration, and their distribution between metastatic and non-metastatic lymph nodes can contribute to a better understanding of the underlying pathological processes. Particular attention should be given to the innate immune system cells and their implication in antigen presentation. Our findings suggest that identifying immunological profiles of lymph nodes may provide a rationale for treatment de-escalation protocols and raise the question of lymph node preservation in antitumor immune responses. However, the heterogeneity and bias assessment of the included studies warrant a cautious interpretation of these findings. Another important limitation is the limited number of studies comparing the immune microenvironment of primary tumors and lymph nodes.

Background/Objectives: Recent studies suggest Metformin could be a potential anti-tumoral agent. This review aims to understand the biological anti-tumoral mechanisms of Metformin in head and neck cancer squamous cell carcinomas (HNSCC) both in vitro and in vivo. Methods: Two investigators screened publications on the biological anti-tumoral effects of Metformin in HNSCC. The literature search was conducted on PubMed, Cochrane Library, and Scopus using PICOTS and PRISMA statements. Results: A total of 30 papers were identified, including 18 studies exploring the effect of Metformin alone and 12 studies exploring its effect in association with another drug or therapy for HNSCC lines. The results suggest that Metformin decreases the proliferation rate of HNSCC through inhibition of cell proliferation by the induction of G0/G1 cell cycle arrest and activation of apoptosis, by regulating proteins involved in carcinogenesis pathways, and also affects the tumor microenvironment by switching the metabolism and activating immune cells. In addition, Metformin can potentiate the efficiency and/or sensibility of other anti-tumoral treatments. The present systematic review highlights the biological anti-tumoral effects of Metformin used alone or in combination with traditional therapies for HNSCC. Conclusions: This review of the literature summarizes the biological anti-tumoral effects associated with Metformin alone or in combination with other therapies. While the molecular effects of Metformin on signaling pathways are different when used alone than in combination, they converge in a decreased proliferation of tumor cells and/or a sensitization of HNSCC to other anti-cancer therapies.

Purpose The neutrophil-to-lymphocyte ratio (NLR) is the most widely biomarker used to assess the inflammatory system in various solid cancers. An elevated NLR has been reported to be associated with worse outcomes in head and neck squamous cell cancers (HNSCC). However, questions remain about the prognostic value of these findings in HNSCC patients with lung metastasis. This study aims to quantify the prognostic impact of NLR on HNSCC patients with lung metastasis. Methods A retrospective chart review of 169 HNSCC patients was performed at the Otorhinolaryngology and the Stomatology and Maxillofacial Surgery Department (Saint-Pierre Hospital), between 2000 and 2017. All patients were divided into two subgroups. Patients who developed lung involvement were assigned to the lung-metastasis-group (LM-group) in contrast to no-lung-metastasis-group patients (NLM-group). The prognostic significance of NLR was evaluated using multivariable analysis adjusting for overall-survival (OS) and lung-metastasis-free-survival (LMFS). Results 95 patients were enrolled in the NLM-group while 74 were in the LM-group. Multivariable analysis highlights that patients with a higher NLR value had shortened OS in the NLM subgroup (HR 1.3; p = 0.024). However, this association was not found in the LM subgroup. When considering both subgroups, an elevated NLR was reported as a prognostic factor of poor LMFS (HR 1.65; p = 0.047). Conclusion Our data revealed that pretreatment NLR is an independent prognostic factor of mortality and lung metastasis development. However, the prognostic value of NLR is not confirmed in patients who suffered from lung metastasis. Physicians should integrate these findings in their treatment algorithm approach. Level of evidence 4