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Seminar

Wednesday, 11th, September 2019
11h
Centre de Recherche - Paris - Amphithéâtre Constant-Burg - 12 rue Lhomond, Paris 5e

Tissue-resident memory CD8+ T cells: new orchestrators of anti-tumor immunity

Tissue-resident memory CD8+ T (Trm) cells stably reside in lymphoid and non-lymphoid tissues, where they mediate potent local innate and adaptive immune responses. Emerging evidence indicates that Trm cells develop in human solid cancers and play a key role in controlling tumor growth. However, the precise mechanisms by which Trm cells mediate anti-tumor immunity is poorly understood. We demonstrated that intradermal administration of gene- or protein-based vaccines efficiently induces specific Trm cell responses against models of tumor-specific and self-antigens, which accumulated in vaccinated and distant non-vaccinated skin. Vaccination-induced Trm cells were largely resistant to in vivo intravascular staining and antibody-dependent depletion. Intradermal, but not intraperitoneal vaccination, generated memory precursors expressing skin-homing molecules in circulation and Trm cells in skin. Interestingly, vaccination-induced Trm cell responses strongly suppressed the growth of cutaneous tumors, independently of circulating memory CD8+ T cells. In addition, antigen-specific activation of skin Trm cells leads to maturation and migration to draining lymph nodes of cross-presenting dermal DCs. Tumor rejection mediated by Trm cells triggers the spread of cytotoxic CD8+ T cell responses against tumor-derived neo- and self-antigens via dermal DCs. These responses suppress the growth of distant intradermal tumors and disseminated melanoma lacking the Trm cell-targeted epitope. Moreover, analysis of RNA sequencing data from human melanoma tumors reveals that enrichment of a Trm cell gene signature associates with DC activation and improved survival. Our work unveils the ability of Trm cells to mediate anti-tumor immunity and amplify the breath of cytotoxic CD8+ T cell responses through DCs.

 

List of 5 selected publications

Resident memory CD8+ T cells amplify anti-tumor immunity by triggering antigen spreading through dendritic cells. Menares E, Gálvez-Cancino F, Cáceres-Morgado P, Ghorani E, López E, Díaz X, Saavedra-Almarza J, Figueroa DA, Roa E, Quezada SA, Lladser A*. Nature Communications, Accepted

Vaccination-induced skin-resident memory CD8+ T cells mediate strong protection against cutaneous melanoma. Gálvez-Cancino F, López E, Menares E, Díaz X, Flores C, Cáceres P, Hidalgo S, Chovar O, Alcántara-Hernández M, Borgna V, Varas-Godoy M, Salazar-Onfray F, Idoyaga J, Lladser A*. Oncoimmunology. 2018 Mar 19;7(7):e1442163.

The function and dysfunction of memory CD8+ T cells in tumor immunity. Reading JL, Gálvez-Cancino F, Swanton C, Lladser A, Peggs KS, Quezada SA. Immunol Rev. 2018 May;283(1):194-212

Caveolin-1 Expression Increases upon Maturation in Dendritic Cells and Promotes Their Migration to Lymph Nodes Thereby Favoring the Induction of CD8+ T Cell Responses. Oyarce C, Cruz-Gomez S, Galvez-Cancino F, Vargas P, Moreau HD, Diaz-Valdivia N, Diaz J, Salazar-Onfray FA, Pacheco R, Lennon-Dumenil AM, Quest AFG, Lladser A*. Front Immunol. 2017 Dec 13;8:1794

Cripto-1 vaccination elicits protective immunity against metastatic melanoma. Ligtenberg MA, Witt K, Galvez-Cancino F, Sette A, Lundqvist A, Lladser A*, Kiessling R*. Oncoimmunology. 2016 Jan 8;5(5):e1128613

Speaker(s)

Alvaro Lladser

Laboratory of Immunoncology, Fundación Ciencia & Vida, Santiago, Chile

Invited by

Ana-Maria Lennon
Domain 3 - U932 - Immunity and Cancer

Institut Curie

Eliane Piaggio
Domain 3 - U932 - Immunity and Cancer

Institut Curie

Contact

Ana-Maria Lennon

Institut Curie

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Dr. Lladser obtained his bachelor degree and professional title from University of Chile. In 2007, he obtained his PhD in Biomedical Sciences from the Faculty of Medicine of the same university. He pursued his postdoctoral training for three years at the Cancer Center Karolinska (CCK), Karolinska Institutet, working with Dr. Rolf Kiessling on developing novel antitumor vaccines. In late 2011, Dr. Lladser initiated his career as independent scientist at the Fundacion Ciencia & Vida as Principal Investigator of the Laboratory of Immunoncology. His research is focused on studying cytotoxic CD8+ T cell-mediated antitumor immunity and how to harness these immune responses for cancer immunotherapy. His current goal is to decipher the role of memory CD8+ T cells in controlling local and disseminated metastatic tumors. Dr. Lladser has supervised 5 PhD theses, 7 Magister theses and 10 undergraduate theses. He has published >30 scientific articles indexed in Pubmed. He has been funded by CONICYT, FONDECYT, FONDEF and CORFO (8 grants). Dr. Lladser also participates as peer reviewer of grant proposals (CONICYT, FONDECYT study section Biología 2) and different scientific journals.