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Background: Vulvar squamous cell carcinoma (VSCC) is a rare cancer for which the cornerstone of treatment is surgery with high complication rates. The unmet need is a less radical and more effective treatment for VSCC., Primary Objectives: To investigate the impact of mono-immunotherapy pembrolizumab as neoadjuvant treatment for primary resectable VSCC patients., Study Hypothesis: Some primary VSCC patients display a specific immune profile which is associated with better survival. In other tumors, this profile is associated with a better response to programmed cell death protein 1 (PD-1) checkpoint blockade which may reinvigorate tumor-specific T cells. This potentially results in a reduced tumor load and less radical surgery and/or adjuvant treatment in patients with this immune profile., Trial Design: This is an investigator-initiated, prospective, single arm, multicenter, phase II clinical trial., Inclusion Criteria: Patients with VSCC clinical stage International Federation of Gynecology and Obstetrics (FIGO) I-III (2021) eligible for primary surgery, with at least one measurable lesion of at least one dimension ≥10 mm in the largest diameter, are included in this study., Main Exclusion Criteria: Patients not suitable for surgery and/or previously treated with immunomodulatory agents, and/or who suffer from comorbidities that may interfere with PD-1 blockade, are excluded from the study., Endpoints: The clinical efficacy of neoadjuvant pembrolizumab in VSCC is measured by an objective change in tumor size according to the Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1) and documented by calipers using standardized digital photography with a reference ruler. In addition, the activation, proliferation, and migration of T cells in the tumor will be studied. The secondary endpoints are pathological complete responses at the time of surgery, feasibility, and safety., Sample Size: 40 patients with FIGO I-III (2021) primary VSCC will be enrolled., Estimated Dates for Completing Accrual and Presenting Results: The intervention phase started in July 2023 and will continue until July 2025. The expected completion of the entire study is July 2026., Trial Registration Number: NCT05761132., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2024. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

The accumulation of tumor-specific CD4 + and CD8 + effector T cells is key to an effective antitumor response. Locally, CD4 + T cells promote the recruitment and effector function of tumor-specific CD8 + T cells and activate innate killer cells in the tumor. Here, we show that tumor-specific CD4 + T cells were predominantly present in the CD39 + subset of tumor-infiltrating lymphocytes (TIL). The CD39 + CD4 + and CD8 + TILs were detected in three different tumor types, and displayed an activated (PD-1 + , HLA-DR + ) effector memory phenotype. CD4 + CD39 + single-cell RNA-sequenced TILs shared similar well-known activation, tissue residency, and effector cell-associated genes with CD8 + CD39 + CD103 + TILs. Finally, analysis of directly ex vivo cell-sorted and in vitro expanded pure populations of CD39-positive and negative CD4 + and CD8 + TILs revealed that tumor-specific antigen reactivity was almost exclusively detected among CD39 + cells. Immunotherapy of cancer is based on the activation of tumor-reactive CD4 + and CD8 + T cells. We show that the expression of CD39 can be used to identify, isolate, and expand tumor-reactive T-cell populations in cancers., (©2020 American Association for Cancer Research.)

This case report presents three cases of Meigs' syndrome: a benign ovarian tumor with ascites and a hydrothorax. After removal of the ovarian tumor, the symptoms resolved and the patients became asymptomatic. In daily practice, Meigs' syndrome is at first sight often mistaken for ovarian cancer. With this case report we would like to emphasize that the clinical presentation of an ovarian tumor might be ovarian cancer, but can masquerade as something uncommon like Meigs' syndrome. In a time span of two years we encountered three cases.