Induction chemotherapy with cemiplimab in a patient with coexistent vulvar cancer and autoimmune disease: A case report.

There is limited data regarding the use of immunotherapy for patients with vulvar squamous cell carcinoma and coexisting autoimmune disease. Cemiplimab is a PD-1 inhibitor approved for use in patients with locally advanced and metastatic cutaneous squamous cell carcinoma. However, little is known about its efficacy in the setting of vulvar cancer. We present a case of advanced vulvar squamous cell carcinoma treated with induction chemotherapy and immunotherapy with cemiplimab followed by definitive chemoradiation in the setting of multiple autoimmune diseases. She achieved a complete clinical response and experienced no worsening of her autoimmune conditions despite cessation of her immunosuppressants and initiating an immune checkpoint inhibitor. We review existing data on neoadjuvant treatment of vulvar cancer and the use of cemiplimab in genital and inguinal squamous cell carcinomas. Ongoing exploration of cemiplimab's efficacy in vulvar cancer and safety in immunosuppressed patients is critical.

Computational pathology identifies immune-mediated collagen disruption to predict clinical outcomes in gynecologic malignancies.

BACKGROUND: The role of immune cells in collagen degradation within the tumor microenvironment (TME) is unclear. Immune cells, particularly tumor-infiltrating lymphocytes (TILs), are known to alter the extracellular matrix, affecting cancer progression and patient survival. However, the quantitative evaluation of the immune modulatory impact on collagen architecture within the TME remains limited. METHODS: We introduce CollaTIL, a computational pathology method that quantitatively characterizes the immune-collagen relationship within the TME of gynecologic cancers, including high-grade serous ovarian (HGSOC), cervical squamous cell carcinoma (CSCC), and endometrial carcinomas. CollaTIL aims to investigate immune modulatory impact on collagen architecture within the TME, aiming to uncover the interplay between the immune system and tumor progression. RESULTS: We observe that an increased immune infiltrate is associated with chaotic collagen architecture and higher entropy, while immune sparse TME exhibits ordered collagen and lower entropy. Importantly, CollaTIL-associated features that stratify disease risk are linked with gene signatures corresponding to TCA-Cycle in CSCC, and amino acid metabolism, and macrophages in HGSOC. CONCLUSIONS: CollaTIL uncovers a relationship between immune infiltration and collagen structure in the TME of gynecologic cancers. Integrating CollaTIL with genomic analysis offers promising opportunities for future therapeutic strategies and enhanced prognostic assessments in gynecologic oncology.

The role of cells that are part of our immune system in altering the structure of the protein collagen within cancers is not fully understood, particularly within cancers that affect women such as ovarian, cervical and uterine cancers. Here, we developed a computer-based method called CollaTIL to explore how immune cells influence collagen in these tumors and affect their growth. We found that a higher presence of immune cells leads to less organized collagen in the tumor. Conversely, when there are fewer immune cells, the collagen tends to be more structured. Additionally, CollaTIL identifies patterns that predict patient outcomes in these cancers. These findings not only enhance our understanding of tumor biology but also may be useful in helping clinicians to predict which patients are at risk of their disease progressing.

Condyloma lata mimicking vulvar carcinoma in an immunocompromised patient: A case report.

Background: Syphilis is a sexually transmitted infection with increasing incidence in the United States. Presentations of syphilis vary widely and can be easily mistaken for other diagnoses, including cancer, especially in atypical cases. Case description: At her delivery after no prenatal care, a 35-year-old woman was found to have exophytic vulvar and perianal lesions, inguinal lymphadenopathy, and a new diagnosis of HIV, with a strong clinical concern for vulvar and/or anal carcinoma. She was subsequently diagnosed with presumed late latent syphilis and began weekly intramuscular penicillin G benzathine treatment. CT imaging demonstrated a perineal plaque-like area with bilateral inguinal, external iliac and retroperitoneal lymphadenopathy. She was seen in gynecologic oncology clinic one week after her initial presentation with notable improvement in the vulvar lesions, raising suspicion for condyloma lata rather than invasive or preinvasive disease on the vulva, however concern remained for dysplasia in the perianal lesion. Another week later, she underwent an exam under anesthesia with vulvar and perianal biopsies revealing chronic inflammation and granulomatous change without evidence of malignancy or dysplasia. At the four week post operative visit, there was almost complete resolution of the lesions. Conclusion: Syphilis should be considered in the differential diagnosis of atypical vulvar lesions.

Surveillance of gynecologic cancer patients post-COVID-19 vaccine: Are CA-125 levels reliable?

Objective: The COVID-19 vaccine is known to instigate an inflammatory response that impacts cancer testing. We aimed to evaluate carbohydrate antigen 125 (CA-125) trends in gynecologic oncology patients in surveillance following COVID-19 vaccination to inform clinical practice. Methods: This was a single institution retrospective study of patients who received a COVID-19 vaccine while undergoing surveillance of gynecologic cancers with serial serum CA-125 measurements. CA-125 levels from the three months before and after vaccination were included in analysis. Differences between mean and median pre- and post-vaccination CA-125 levels for each patient were calculated. The mean and median of these differences were calculated, as well as the distribution of change. Demographic and cancer-related variables were also recorded. Results: Twenty-six patients who received a COVID-19 vaccine and were followed with surveillance serum CA-125 levels were identified. The mean age was 68.2 years; 92 % received a two-vaccine series. Forty-six percent had endometrial cancer and 54 % had ovarian cancer. The mean change from pre- to post-vaccine mean CA-125 level was 0.16 (±7.17) U/mL and the median change from pre- to post-vaccine median CA-125 level was -0.30 (IQR 3.66) U/mL. The range in change from pre- to post-vaccine mean was -16.50 to 24.00 U/mL, with 73 % of patients between -4 and +4 U/mL. Conclusion: We found no clinically significant change in CA-125 level after patients under surveillance for gynecologic cancers were vaccinated against COVID-19, suggesting that that the vaccine does not impact the utility of CA-125 as a tool to monitor disease in this population.

Sensing of Bacterial Cyclic Dinucleotides by the Oxidoreductase RECON Promotes NF-κB Activation and Shapes a Proinflammatory Antibacterial State.

Bacterial and host cyclic dinucleotides (cdNs) mediate cytosolic immune responses through the STING signaling pathway, although evidence suggests that alternative pathways exist. We used cdN-conjugated beads to biochemically isolate host receptors for bacterial cdNs, and we identified the oxidoreductase RECON. High-affinity cdN binding inhibited RECON enzyme activity by simultaneously blocking the substrate and cosubstrate sites, as revealed by structural analyses. During bacterial infection of macrophages, RECON antagonized STING activation by acting as a molecular sink for cdNs. Bacterial infection of hepatocytes, which do not express STING, revealed that RECON negatively regulates NF-κB activation. Loss of RECON activity, via genetic ablation or inhibition by cdNs, increased NF-κB activation and reduced bacterial survival, suggesting that cdN inhibition of RECON promotes a proinflammatory, antibacterial state that is distinct from the antiviral state associated with STING activation. Thus, RECON functions as a cytosolic sensor for bacterial cdNs, shaping inflammatory gene activation via its effects on STING and NF-κB.