The clinical spectrum of coronavirus disease 2019 is getting wider with the exponential increase of patients worldwide. Initially described with flu-like symptoms, variable cutaneous manifestations have been reported, with only few histopathological descriptions. Detection of the virus in cutaneous samples has been assessed in very few cases until now, and the causative role of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has not been proven for every type of cutaneous manifestations yet. We aimed to describe histological features of cutaneous eruptions occurring concomitantly to SARS-CoV-2 infection and assess by immunochemistry and in situ hybridization using RNAscope validation techniques the presence of the virus in skin lesions. We retrieved all skin biopsies received in the departments of pathology and dermatopathology, University Hospital of Strasbourg, performed in hospitalized SARS-CoV-2–infected patients presenting concomitant cutaneous manifestations since March 2020. In situ hybridization and immunostaining using a polyclonal SARS nucleocapsid protein antibody were performed on each sample. Skin biopsies from six patients presenting morbilliform eruption concomitant to SARS-CoV-2 infection were available for evaluation. All six samples showed varying degrees of spongiosis, perivascular inflammatory infiltrates of the dermis, and, for some of them, discrete interface dermatitis. In situ hybridization and immunohistochemistry were negative in all cutaneous samples. Morbilliform rash concomitant to SARS-CoV-2 infection is characterized by mild and unspecific histopathological features with no detectable viral RNA and protein and appears then not to be directly caused by the virus. Even if, at least for a few cases, the differential diagnosis with drug hypersensitivity reaction can be difficult, these cutaneous eruptions seem to rather correspond to paraviral rashes.

No abstract

A nonsmoker man in his 40s underwent bilateral lung transplantation with a referral diagnosis of genetic-related idiopathic pulmonary fibrosis (IPF). The patient had no medical history in childhood and early adulthood, nor was there a family history of IPF. His nonsmoker

No abstract

No abstract

No abstract

Immune checkpoint inhibitors (ICI) represent the cornerstone for treatment of patients with metastatic clear-cell renal cell carcinoma (ccRCC). Despite a favorable response for a subset of patients, others experience primary progressive disease highlighting the need to precisely understand plasticity of cancer cells and their crosstalk with the microenvironment to better predict therapeutic response and personalize treatment. Single-cell RNA sequencing of ccRCC at different disease stages and normal adjacent tissue (NAT) from patients identified 46 cell populations, including 5 tumor subpopulations, characterized by distinct transcriptional signatures representing an epithelial to mesenchymal transition gradient and a novel inflamed state. Deconvolution of the tumor and microenvironment signatures in public datasets and in data from the BIONIKK clinical trial (NCT02960906) revealed a strong correlation between mesenchymal-like ccRCC cells and myofibroblastic cancer-associated fibroblasts (myCAFs), which are both enriched in metastases and correlate with poor patient survival. Spatial transcriptomics and multiplex immune staining uncovered spatial proximity of mesenchymal-like ccRCC cells and myCAFs at the tumor-NAT interface. Moreover, enrichment in myCAFs was associated with primary resistance to ICI therapy in the BIONIKK clinical trial. This data highlights the epithelial-mesenchymal plasticity of ccRCC cancer cells and their relationship with myCAFs, a critical component of the microenvironment associated with poor outcome and ICI resistance.

Purpose: Immune checkpoint inhibitors (ICI) represent the cornerstone for treatment of patients with metastatic clear-cell renal cell carcinoma (ccRCC). Despite a favourable response for a subset of patients, others present primary progressive disease highlighting the need to better understand plasticity of cancer cells and their crosstalk with the microenvironment to better predict therapeutic response and personalize treatment. Experimental design: We performed single-cell RNA sequencing on 56,421 cells from tumour and normal adjacent tissue of patients with ccRCC at different disease stages. Identification of cancer and microenvironment cell populations was validated by deconvolution analyses of public datasets and their localizations within tumours were determined by spatial transcriptomic analyses. We also assessed association of tumour and microenvironment populations with response of ICI treated patients using data from the BIONIKK clinical trial (NCT02960906). Results: We identify 46 cell populations including 5 tumour subpopulations characterized by distinct transcriptional signatures representing an epithelial to mesenchymal transition gradient as well as novel inflamed state. Deconvolution of the tumour and microenvironment signatures revealed strong correlation between mesenchymal-like ccRCC cancer cells and myofibroblastic cancer-associated fibroblasts (myCAFs) that associate with metastasis and tumour aggressiveness. Spatial transcriptomics revealed their co-localization and we identified therapeutically targetable ligand-receptor interactions underlying their crosstalk. Finally, we show that enrichment in myCAFs was associated with primary resistance to ICI therapy in the BIONIKK clinical trial. Conclusions: We describe epithelial-mesenchymal plasticity of ccRCC cancer cells and identify potentially targetable pathways involved in tumour cell-myCAFs crosstalk opening the way for personalized treatment of ccRCC patients. Citation Format: Alexandra Helleux, Guillaume Davidson, Yann A. Vano, Véronique Lindner, Antonin Fattori, Marie Cerciat, Reza T. Elaidi, Virginie Verkarre, Cheng-Ming Sun, Christine Chevreau, Mostefa Bennamoun, Hervé Lang, Thibault Tricard, Wolf H. Fridman, Catherine Sautes-Fridman, Xiaoping Su, Damien Plassard, Céline Keime, Christelle Thibault-Carpentier, Philippe Barthelemy, Stéphane Oudard, Irwin Davidson, Gabriel G. Malouf. Roles of mesenchymal-like tumour cells and myofibroblastic cancer-associated fibroblasts in progression and therapeutic response of clear-cell renal cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1342.