SANCHEZ-ELSNER, Tilman;UNIVERSITY OF SOUTHAMPTON;CLARKE, James;GANESAN, Anusha Preethi;VIJAYANAND, Pandurangan;OTTENSMEIER, Christian;LA JOLLA INSTITUTE FOR ALLERGY AND IMMUNOLOGY
Global transcriptional profiling of CTLs in tumors and adjacent non- tumor tissue from treatment-naive patients with early stage lung cancer revealed molecular features associated with robustness of anti -tumor immune responses. Major differences in the transcriptional program of tumor-infiltrating CTLs were observed that are shared across tumor subtypes. Pathway analysis revealed enrichment of genes in cell cycle, T cell receptor (TCR) activation and co-stimulation pathways, indicating tumor-driven expansion of presumed tumor antigen-specific CTLs. Marked heterogeneity in the expression of molecules associated with TCR activation and immune checkpoints such as 4-lBB, PDl, TIM3, was also observed and their expression was positively correlated with the density of tumor-infiltrating CTLs. Transcripts linked to tissue-resident memory cells (TRM), such as CD 103, were enriched in tumors containing a high density of CTLs, and CTLs from CD 103high tumors displayed features of enhanced cytotoxicity, implying better anti -tumor activity. In an independent cohort of 689 lung cancer patients, patients with CD103high (TRM rich) tumors survived significantly longer. In summary, the molecular fingerprint of tumor-infiltrating CTLs at the site of primary tumor was defined and a number of novel targets identified that appear to be important in modulating the magnitude and specificity of anti-tumor immune responses in lung cancer.Un profilage transcriptionnel global des lymphocytes T cytotoxiques (CTL pour Cytotoxic T Cell) dans des tumeurs et un tissu non tumoral adjacent provenant de patients naïfs de tout traitement atteints d'un cancer du poumon à un stade précoce a révélé des caractéristiques moléculaires associées à la robustesse des réponses immunitaires antitumorales. Des différences importantes dans le programme de transcription des lymphocytes T cytotoxiques infiltrant les tumeurs ont été observées, lesquelles sont partagées à travers des sous-types de tumeur. Une analyse
