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Abstract Objective: The average age of patients with vulvar squamous cell carcinoma (SCC) has been reported to have declined. Human papilloma virus (HPV)-related lesions have been shown to be associated with the expression of the immunohistochemical (IHC) marker p16. Non-HPV-related tumors have been characterized by p53 abnormal expression and PDL1 expression. We aimed to evaluate the correlation between these markers and vulvar SCC and to relate it to the clinical and pathological characteristics. Methods: Histopathologic assessments and IHC analyses of p16, p53, and PDL1 were performed in 41 samples of vulvar SCC collected between 2016 and 2021. The data were correlated with clinical and pathological characteristics of the patients. Results: The mean age of the patients was 72.1 years. Positive p16 and PDL1 staining was detected in 24.4% and 17.1% of the samples, respectively. p53 expression was negative in 19.5% of the samples, whereas it was overexpressed in 24.4%. p16-positive tumors showed a smaller depth of invasion (DOI) (p = 0.014), while tumors with p53 abnormal expression showed greater DOI (p = 0.041). PDL1 expression was correlated with increased number of inflammatory cells (p = 0.055). In addition, lesions with lymphovascular space invasion were p16-negative. Conclusion: In our sample, regarding to the SCC incidence the patients’ mean age did not change. The expression of p16 was inversely correlated with p53 results. Tumors with p53 abnormal expression and absence of p16 showed a greater DOI. Our data suggest an association between PDL1 expression and increased inflammatory infiltrates in vulvar SCC.

Introduction: In autoimmune diseases, autoreactive B cells comprise only the 0.1-0.5% of total circulating B cells. However, current first-line treatments rely on non-specific and general suppression of the immune system, exposing patients to severe side effects. For this reason, identification of targeted therapies for autoimmune diseases is an unmet clinical need. Methods: Here, we designed a novel class of immunotherapeutic molecules, Bi-specific AutoAntigen-T cell Engagers (BiAATEs), as a potential approach for targeting the small subset of autoreactive B cells. To test this approach, we focused on a prototype autoimmune disease of the kidney, membranous nephropathy (MN), in which phospholipase A2 receptor (PLA2R) serves as primary nephritogenic antigen. Specifically, we developed a BiAATE consisting of the immunodominant Cysteine-Rich (CysR) domain of PLA2R and the single-chain variable fragment (scFv) of an antibody against the T cell antigen CD3, connected by a small flexible linker. Results: BiAATE creates an immunological synapse between autoreactive B cells bearing an CysR-specific surface Ig+ and T cells. Ex vivo , the BiAATE successfully induced T cell-dependent depletion of PLA2R-specific B cells isolated form MN patients, sparing normal B cells. Systemic administration of BiAATE to mice transgenic for human CD3 reduced anti-PLA2R antibody levels following active immunization with PLA2R. Discussion: Should this approach be confirmed for other autoimmune diseases, BiAATEs could represent a promising off-the-shelf therapy for precision medicine in virtually all antibody-mediated autoimmune diseases for which the pathogenic autoantigen is known, leading to a paradigm shift in the treatment of these diseases. [ABSTRACT FROM AUTHOR]

The correction notice in the journal "Frontiers in Immunology" addresses typographical errors in the Methods section of an article on targeted immunotherapy for autoreactive B cell depletion in autoimmune diseases. The correction involves clarifying the construction of targeting vectors for homologous recombination in embryonic stem cells, specifically related to humanizing CD3 genes in mice. The authors acknowledge the error and emphasize that it does not impact the scientific conclusions of the original article. [Extracted from the article]