Probes for CD8

Cemiplimab is approved for the treatment of locally advanced basal cell carcinomas (BCCs), however with mitigated results. We sought to interrogate the cellular and molecular transcriptional reprogramming underlying BCC resistance to immunotherapy.Here, we combined spatial and single-cell transcriptomics to deconvolute the spatial heterogeneity of the tumor microenvironment in regard with response to immunotherapy, in a cohort of both naive and resistant BCCs.We identified subsets of intermingled cancer-associated fibroblasts (CAFs) and macrophages contributing the most to CD8 T cells exclusion and immunosuppression. Within this spatially-resolved peritumoral immunosuppressive niche, CAFs and adjacent macrophages were found to display Activin A-mediated transcriptional reprogramming towards extracellular matrix remodeling, suggesting active participation to CD8 T cells exclusion. In independent datasets of human skin cancers, Activin A-conditioned CAFs and macrophages were associated with resistance to immune checkpoint inhibitors (ICI).Altogether, our data identify the cellular and molecular plasticity of TME and the pivotal role of Activin A in polarizing the TME towards immune suppression and ICI resistance.

Context.-The World Health Organization has recently recognized lymphoepithelioma-like carcinoma, or inflammatory hepatocellular carcinoma, as a variant of hepatocellular carcinoma. Objective.-To identify and characterize the inflammatory hepatocellular carcinomas in our institution from 1988 to the present. Design.-All cases of hepatocellular carcinoma in our institution from 1988 to the present were reviewed and reclassified as lymphoepithelioma-like carcinoma and were studied in comparison to appropriately matched controls. Results.-Among the 8 cases of lymphoepithelioma-like carcinoma identified, the male to female ratio was 1:3, the mean age was 68.5 years (range, 57-78 years), and all of the cases were seen in noncirrhotic livers. The average numbers of lymphocytes were significantly higher in the cases than in the controls. T cells were predominant, with a uniform distribution of CD4 and CD8 positive cells. Cholangiolar differentiation was seen by K19 positivity as focal in 1 case and diffuse in 2 cases. In situ hybridization for Epstein-Barr virus was negative in all of the cases. Diffuse overexpression of p16 (>75% of cells) was seen in 2 cases, both of which were negative for the presence of transcriptionally active human papilloma virus by in situ hybridization. In our series, 3 of 8 cases (37.5%) showed local recurrence, which was similar to the controls (6 of 18; 33%), P > .99. Although the rate of distant metastases was lower among the cases (12.5%) than the controls (22.2%), the difference was not statistically significant (P > .99). Conclusion.-We present the first series of 8 cases of lymphoepithelioma-like carcinoma of the liver occurring in patients without cirrhosis and with a female preponderance and the absence of Epstein-Barr virus. Although clinical outcomes were similar to those of controls in our small series, additional data may be required for confirmation.