Immunoncology

PROFILE

Cancer is a highly prevalent and deadly disease. Conventional oncological treatments have devastating adverse side effects and are not curative in advanced stages of the disease. We investigate Cancer Immunotherapy, a novel approach that aims to activate the patients’ own immune system, namely cytotoxic T cells, to attack and ultimately eliminate tumors. In particular, we study long-lived “memory” cytotoxic T cells, which can provide long-lasting protection against primary tumors as well as disseminated metastasis. Our research focuses on how to stimulate memory cytotoxic T cells by either using Vaccinesor manipulating these cells in the laboratory and re-injecting them back into patients, so-called Adoptive T Cell Therapy.

LAB MEMBERS

Research Head: Álvaro Lladser

Research Associate: Vincenzo Borgna, MD, PhD

Doctoral students: Evelyn Menares • Sofía Hidalgo • Diego Figueroa

Undergraduate students: Ornella Chovar • Pablo Cáceres • Javiera Gómez • Juan Saavedra

Research assistants: Eduardo Roa • Ximena Díaz

COLLABORATIONS

National Collaborations:
• Dr. Rodrigo Pacheco (Fundación Ciencia & Vida). We are studying how the dopaminergic regulation of cytotoxic CD8+ T cells and dendritic cells affects the antitumor immune response.
• Dr. Daniela Sauma (Faculty of Science, Universidad de Chile). We are studying the role of CD39 and CD73 in the stemness of memory CD8+ T-cells.
• Dr. Manuel Varas (Faculty of Medicine, Universidad de los Andes). We are developing novel tumor models to accurately study the involvement of CD8+ T cells in antitumor immunity.
• Dr. Flavio Salazar (Faculty of Medicine, Universidad de Chile). We are developing T cell-based immunotherapies that can be used in the clinic.
• Dr. Fabiola Osorio (Faculty of Medicine, Universidad de Chile). We collaborate on basic aspects of antigen cross-presentation in antitumor immune responses.

International Collaborations:
• Dr. Rolf Kiessling (Karolinska Institute, Sweden). We have a vast collaboration on developing novel T cell-based vaccines and immunotherapies against cancer.
• Dr. Sergio Quezada (University College London, UK). We have a collaboration studying the dysfunction of memory CD8+ T cells in human tumors and preclinical models.
• Dr. Andreas Lundqvist (Karolinska Institute, Sweden). We have a collaboration to study the interplay between CD8+ T cells and NK cells in antitumor immunity.
• Dr. Eliane Piaggio (Curie Institute, France). We have a collaboration analyzing memory CD8+ T cells in human cancers.

SELECTED PUBLICATIONS

  • Witt K, Ligtenberg MA, Conti L, Lanzardo S, Ruiu R, Wallmann T, Tufvesson-Stiller H, Chambers BJ, Rolny C, Lladser A, Lundqvist A, Cavallo F, Kiessling R. Cripto-1 plasmid DNA vaccination targets metastasis and cancer stem cells in murine mammary carcinoma. Cancer Immunology Research. 2018 Aug 24. pii: canimm.0572.2017. doi: 10.1158/2326-6066.CIR-17-0572. | | ABSTRACT
  • 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*. Vaccination-induced skin-resident memory CD8+ T cells mediate strong protection against cutaneous melanoma. Oncoimmunology. 2018;7(7). Article: e1442163. doi: 10.1080/2162402X.2018.1442163. | | ABSTRACT
  • Reading J, Gálvez-Cancino F, Swanton C, Lladser A, Peggs K, Quezada S. The function and dysfunction of memory CD8+ T cells in tumor immunity. Immunological Reviews. 2018;283(1):194-212. doi: 10.1111/imr.12657. | | ABSTRACT
  • Prado C, Gaiazzi M, González H, Ugalde V, Figueroa A, Osorio-Barrios F, Lopez E, Lladser A, Rasini E, Marino F, Zaffaroni M, Cosentino M, Pacheco R. Dopaminergic stimulation of myeloid antigen-presenting cells attenuates STAT3-activation favouring the development of experimental autoimmune encephalomyelitis. Front Immunol. 2018 Mar 21;9:571. doi: 10.3389/fimmu.2018.00571. eCollection 2018. | | ABSTRACT
  • Flores-Santibáñez F, Cuadra B, Fernández D, Rosemblatt MV, Núñez S, Cruz P, Gálvez-Cancino F, Cárdenas JC, Lladser A, Rosemblatt M, Bono MR, Sauma D. In Vitro-Generated Tc17 Cells Present a Memory Phenotype and Serve As a Reservoir of Tc1 Cells In Vivo. Front Immunol. 2018 Feb 8;9:209. doi: 10.3389/fimmu.2018.00209. eCollection 2018. | | ABSTRACT
  • Murgas P, Bustamante N, Araya N, Cruz-Gómez S, Durán E, Gaete D, Oyarce C, López E, Herrada AA, Ferreira N, Pieringer H, Lladser A. A filamentous bacteriophage targeted to carcinoembryonic antigen induces tumor regression in mouse models of colorectal cancer. Cancer Immunol Immunother. 2018 Feb;67(2):183-193. | | ABSTRACT
  • Varas-Godoy M, Lladser A, Farfan N, Villota C, Villegas J, Tapia JC, Burzio LO, Burzio VA, Valenzuela PDT. In vivo knockdown of antisense noncoding mitochondrial RNAs by a lentiviral-encoded shRNA inhibits melanoma tumor growth and lung colonization. Pigment Cell Melanoma Res. 2018 Jan;31(1):64-72 | | ABSTRACT
  • 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*. 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. Front Immunol. 2017 Dec 13;8:1794. doi: 10.3389/fimmu.2017.01794. eCollection 2017. | | ABSTRACT
  • Gálvez-Cancino F, Roco J, Rojas-Colonelli N, Flores C, Murgas P, Cruz-Gómez S, Oyarce C, Varas-Godoy M, Sauma D, Lladser A*. A short hairpin RNA-based adjuvant targeting NF-κB repressor IκBα promotes migration of dermal dendritic cells to draining lymph nodes and antitumor CTL responses induced by DNA vaccination. Vaccine. 2017 Jul 24;35(33):4148-4154. | | ABSTRACT
  • Figueroa C., Gálvez-Cancino F., Oyarce C., Contreras F., Prado C., Valeria C., Cruz S., Lladser A., Pacheco R. Inhibition of dopamine receptor D3 signaling in dendritic cells increases antigen cross-presentation to CD8+ T-cells favoring anti-tumor immunity. J Neuroimmunol. 303:99-107. doi: 10.1016/j.jneuroim.2016.12.014 (2017). | | ABSTRACT
  • Ligtenberg M. A., Witt K., Gálvez-Cancino F., Sette A., Lladser A., Kiessling R. Cripto-1 vaccination elicits protective immunity against metastatic melanoma. Oncoimmunology 5(5):e1128613, DOI: 10.1080/2162402X.2015.1128613 (2016) | | ABSTRACT
  • Fernandez D., Flores-Santibañez F., Neira J., Osorio F., Tejón G., Nuñez S., Hidalgo Y., Fuenzalida M. J., Meza D., Ureta G., Lladser A., Pacheco R., Acuña-Castillo C., Guixé V., Quintana F. J., Bono M. R., Rosemblatt M., Sauma D. Purinergic signaling as a regulator of Th17 cell plasticity. Plos One 11(6):e0157889. DOI: 10.1371/journal.pone.0157889 (2016) | | ABSTRACT
  • Contreras F., Prado C., González H., Franz D., Osorio-Barrios F., Osorio F., Ugalde V., Lopez E., Elgueta D., Figueroa A., Lladser A., Pacheco R. Dopamine receptor D3 signaling on CD4+ T cells favors Th1- and Th17-mediated immunity. J. Immunol. 196(10):4143 (2016) | | ABSTRACT
  • Ligtenberg M. A., Mougiakakos D., Mukhopadhyay M., Witt K., Lladser A., Chmielewski M., Riet T., Abken H., Kiessling R. Coexpressed catalase protects chimeric antigen receptor-redirected T cells as well as bystander cells from oxidative stress-induced loss of antitumor activity. J. Immunol. 196(2):759 (2016) | | ABSTRACT

PATENTS

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