Cancer stem-like cells evade CD8+CD103+tumor-resident memory T (TRM) lymphocytes by initiating an epithelial-to-mesenchymal transition program in a human lung tumor model

• DOI: 10.1136/jitc-2022-004527
• Publication Date: 2022-04-13T17:32:33Z
• Authors: Stéphanie Corgnac; Isabelle Damei; Gwendoline Gros; Aziza Caidi; Stéphane Terry; Salem Chouaib; Marc Deloger; Fathia Mami-Chouaib
• Keywords: Tumor Antigen

Background Cancer stem cells (CSC) define a population of rare malignant endowed with ‘stemness’ properties, such as self-renewing, multipotency and tumorigenicity. They are responsible for tumor initiation progression, could be associated resistance to immunotherapies by negatively regulating antitumor immune response acquiring molecular features enabling escape from CD8 T-cell immunity. However, the immunological hallmarks human lung CSC their potential interactions resident memory T (T RM ) within microenvironment have not been investigated. Methods We generated non-small cell cancer model, including line clones, autologous + CD103 − non-T dissect out properties susceptibility specific T-cell-mediated cytotoxic activity. Results Unlike parental cells, characterized an epithelial-to-mesenchymal transition program defined upregulation SNAIL1 transcription factor downregulation phosphorylated-GSK-3β surface E-cadherin. Acquisition profile results in partial -cell-mediated cytotoxicity, which correlates decreased expression ligand E-cadherin leukocyte antigen-A2-neoepitope complexes. On other hand, gained intercellular adhesion molecule (ICAM)-1 thereby sensitivity function-associated antigen (LFA)-1-dependent killing. Cytotoxicity is inhibited anti-ICAM-1 anti-major histocompatibility complex class I neutralizing antibodies further emphasizing role LFA-1/ICAM-1 interaction receptor-dependent lytic function. Conclusion Our data support rational design immunotherapeutic strategies targeting optimize responsiveness local more efficient anticancer treatments.