Defining the Tumour Immune Microenvironment in Vulvar Squamous Cell Carcinoma to Guide Treatment Personalisation

Vulvar cancer is a rare gynaecological malignancy managed predominantly by surgery, with currently limited scope for personalised treatment. Approximately 25-35% of patients with apparent early-stage disease harbour nodal metastases, yet the majority still undergo nodal dissection, underscoring the need for better approaches to guide both the extent of surgery and lymph node assessment. Surgical de-escalation and the expansion of therapeutic options, including immune checkpoint inhibitors, antibody-drug conjugates and therapeutic vaccines, are developing areas, but progress depends on identifying reliable biomarkers to guide treatment pathway choice. The tumour immune microenvironment may offer one such tool. Four T-cell defined phenotypes have been described in vulvar squamous cell carcinoma: inflamed, altered-excluded, altered-immunosuppressed, and deserted. Inflamed and altered-excluded (‘hot') tumours show high T-cell infiltration and an immunogenically active microenvironment and are associated with better oncological outcomes after surgery and have been hypothesised to have greater potential for immune checkpoint inhibition and other systemic therapies. Altered-immunosuppressed and deserted (‘cold') tumours represent the area of greatest unmet need, with poorer prognosis and limited therapeutic options. As understanding of vulvar squamous cell carcinoma grows, additional phenotypes are being described, raising the question of how these might inform treatment selection. This narrative review summarises current evidence on the tumour immune microenvironment in vulvar squamous cell carcinoma and generates theories around the potential for the tumour immune microenvironment to guide both surgical and systemic treatment decisions, whilst highlighting key unmet needs in this area.