Decoding and Remodeling the Suppressive Tumor Immune Microenvironment in Head and Neck Cancer

Dear Colleagues,

Tumorigenesis is not only mediated by tumor-intrinsic factors, but also by cell–cell interactions and signaling processes within the tumor immune microenvironment (TIME). The TIME comprises a diverse array of cellular components, including immune cells, cancer-associated fibroblasts (CAFs), neurons, and endothelial cells, in addition to non-cellular elements such as the extracellular matrix, growth factors, cytokines, and metabolites. The immune composition within the TIME can either suppress or promote tumor growth, thereby influencing disease progression and therapeutic response. Immunosuppressive populations such as regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), and tumor-associated macrophages (TAMs) play critical roles in dampening anti-tumor immunity. Growth factors such as vascular endothelial growth factor (VEGF) stimulate angiogenesis, facilitating tumor growth and metastasis. CAFs represent a major stromal component of the TIME, contributing to extracellular matrix remodeling and correlating with poor prognosis across multiple cancer types. Additionally, neurons engage in bidirectional interactions with tumor and immune cells to modulate immune function and promote tumorigenesis. Recent advances in single-cell and spatial technologies have enabled deeper functional and spatial characterization of these intricate interactions within the TIME. This Special Issue will highlight recent progress in the understanding of the TIME in head and neck cancer, with the goal of identifying novel therapeutic strategies and improving responses to current treatment regimens. Key topics will include the following: 

1.  Application of single-cell and spatial technologies to characterize the TIME in head and neck tumors to elucidate mechanisms underlying therapeutic response and resistance.
2. Definition of temporal dynamics of the TIME during treatment to uncover mechanisms driving host response.
3. Identification and validation of novel immune and molecular biomarkers predictive of response to immunotherapy.
4. Leverage of mechanistic insights into the TIME to inform rational design of clinical trials integrating combination immunotherapeutic strategies.
5. Investigation of the role of immunosuppressive myeloid populations in tumor progression and evaluation of potential therapeutic approaches to remodel the TIME.

Dr. Andrew G. Sikora
Dr. Jennifer L. Anderson
Guest Editors

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