Search

Background and Rationale: OSCC is the most frequent head and neck cancer. While it is mainly affecting patients with a smoking and/or alcohol history (SD), 10% to 15% of OSCC are diagnosed in patients with not known risk factors (NSND). We and others have shown that OSCC from NSND patients are characterized by an enrichment in interferon gamma (IFNγ) response and PD-1 signaling pathways together with a higher intratumor T-cell infiltrate. Herein, we seek to gain more insights into the immune and non-immune tumor microenvironment (TME) of OSCC in SD vs. NSND patients. Material and Methods: We made use of single-cell RNA seq (10x Genomics) from non-sorted and CD45 negative enriched cell suspensions of OSCC biopsies from 11 treatment naïve patients, human papillomavirus negative, including 6 SD and 5 NSND patients. Results: All samples were characterized by a strong immune cell infiltrate. Consistent with our previous results, the analysis of 51,629 immune cells confirmed that NSND patients’ samples displayed a significantly higher proportion of T cells (p = 0.005) compared to SD patients. NK cells were also increased, with 2% in SD patients versus 6% in NSND patients (p = 0.008). T cells strongly expressed IFNγ and remarkably, both myeloid cells and tumor cells from NSND patients had an increased enrichment in IFNγ response pathway in NSND as compared to SD patients. The TME of SD patients was characterized by the presence of 15% of plasma cells vs. 3% in NSND patients (p = 0.003). Thus, tumors from NSND versus SD patients represent two distinct groups of tumors characterized by a different immune TME. Moreover, tumors from SD patients displayed 2% vs. 4% Cancer Associated Fibroblasts (CAFs) (p = 0.01). In addition, among CAFs subpopulations, myofibroblast CAFs, defined as the subpopulation producing extracellular matrix proteins were found only in tumors from SD patients, suggesting that distinct CAFs subpopulations may shape the immune TME by affecting the recruitment and function of adaptive immune cells in SD versus NSND patients. Finally, we analyzed tumor cells using non-negative matrix factorization to find Meta Programs (MP), which are set of genes coordinately upregulated. We identified 5 MP associated with different biological functions: epithelial differentiation, stress, cell cycle (G2/M), partial epithelial-to-mesenchymal transition, and epithelial senescence. While the epithelial differentiation MP was found in all patients, the remaining ones were more frequently found in SD patients. Conclusion: Our results show that the TME of OSCC from NSND vs. SD differs in terms of T, NK, and plasma cells composition, CAFs, and tumor cells MP. Integration with spatial transcriptomics is ongoing. Those biological differences may represent an opportunity to refine the therapeutic approaches in the two populations of patients. Citation Format: Yannick Le Meitour, Béatrice Vanbervliet, Sonia Canjura-Rodriguez, Cyril Degletagne, Laurie Tonon, Lucas Michon, Jebrane Bouaoud, Philippe Zrounba, Aude Excoffier, Karène Mahtouk, Pierre Saintigny. Single-cell analysis of oral squamous cell carcinoma (OSCC) from smoker vs. non-smoker patients highlights two groups of tumors with distinct immune microenvironments. [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 4530.

Introduction: Synovial Sarcoma (SS) is a rare and aggressive disease that predominantly occurs in young adult. SS are characterized by a pathognomonic t(X:18) translocation leading SS18: SSX1/2/4 fusion. Small studies (n Methods: We present a clinico-biological cohort study including all adult patients with histologically confirmed diagnosis of afvanced SS from January 2000, registered in the French Sarcoma database (NETSARC+) and with available formalin-fixed paraffin embedded (FFPE) archival tumor samples and clinical data. FFPE tumor samples were analyzed by dedicated whole-exome RNA-sequencing (WERS) to assess transcriptomic, small nucleotide variation (SNV) and fusions. Results: 122 patients (133 samples) met the study criteria, including 11 patients with paired primary-metastatic tumor samples. Clinical characteristics (age, sex, tumor grade, primary and metastasis site distribution) were consistent with expected SS population. The SS18:SSX1/2/4 fusion was found in all patient (90% by WERS and if negative, by FISH). Unsupervised analyses of transcriptomic data by principal component analyses, hierarchical sample clustering or UMAP revealed heterogeneity in gene expression. Clinical factors (age, sex, grade, tumor type, complete response to treatment, survival) did not correlate with transcriptomic profiles. Immune cell analyses confirmed a low infiltration of immune cells, notably poor in CD8+ T cells. Cancer testis antigens such as NYESO-1, MAGE-A4 were both expressed with a heterogeneous co-expression of other CTAs across samples. In the 11 primary-metastatic paired- samples, no gene pathway was found differentially expressed between primary and metastatic samples cohort with the exception of lung tissue specific genes. Comparing chemotherapy-naïve versus pre-treated samples did not identify differential expression of specific genes across samples. Single Nucleotide Variant analyses was reliable on 84% FFPE samples and revealed an overall low Tumor Mutational Burden with some samples harboring canonical oncogene pathogenic mutations of BTK, RAS, NF1, RB1 as well as in DNA repair pathway(15% spanning over ATM ATR,CHK2, BRCA1/2 PALB2 CHK2, FANCM, RAD51), PI3K pathways (PI3KCA E545K) and other poorly described in SS. Conclusion: Investigating the largest cohort of metastatic SS by whole-exome RNA-sequencing, revealed Synovial Sarcoma, usually classified as “simple genomic sarcoma” is a translocation-related sarcoma harboring heterogeneous transcriptomic and numerous SNV co-alterations including targetable mutations. Citation Format: Helene Vanacker, Mehdi Brahmi, Yannick Le Meitour, Julien Bollard, Valery Attignon, Alexandra Meurgey, Myriam Jean-Denis, Laurie Tonon, Shibani Pokras, Erika Klohe, Michael Nathenson, Kristin Blouch, Ioanna Eleftheriadou, Jean-Yves Blay, Franck Tirode, Armelle Dufresne. Whole-exome RNA sequencing of metastatic synovial sarcomas reveals heterogeneous transcriptomic profile and targetable co-alterations: Cohort study from the French Sarcoma Group. [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 6071.

Mechanical commutator (40) for electric machine (1) suitable for supplying power via a polyphase current system comprising q phases, where q is a positive integer strictly greater than 1, to a rotary electric machine rotor (3) having 2*p magnetic poles, comprising: - a slip ring (41) that rotates about an axis (X) of the electric machine (X), of elementary pattern equal to 2*π/(p*q); - at least one pair radially extending brushes, a positive brush (45) and a negative brush (46), suitable for rubbing against the slip ring (41), which are rotatably fixed and each defined over an angular sector, and suitable for connection to one and the same voltage source, in particular a vehicle battery (B), characterized in that the mechanical slip ring (41) comprises n*p*q, where in particular n = 1 or n = 2, conductive strips (60) which come one after the other circumferentially, each strip (60) being defined over an angular sector, adjacent strips being isolated from one another, the strips being distributed in q groups (a', b', c'), all of the strips (60) of one and the same group being electrically connected to one another, the q groups alternating circumferentially, and in that the brushes (45, 46) of one and the same pair are circumferentially offset relative to one another by [(2k+1)*2*π]/(2*p)], k being a natural integer.