Profile
Cancer is a group of deadly diseases characterized by the uncontrolled growth of abnormal cells in the body. Conventional oncological treatments have severe adverse side effects and are not curative in advanced stages of the disease. We investigate how the immune system, mainly through cytotoxic T cells, can recognize and attack cancer cells. In particular, we study long-lived “memory” cytotoxic T cells, which can provide long-lasting immunity against solid tumors as well as disseminated cancers. We also seek to harness this knowledge to improve cancer immunotherapy, a novel approach that aims to activate the patients’ own cytotoxic T cells to eliminate cancer cells. Our research focuses on how to stimulate memory cytotoxic T cells by either using vaccines or manipulating these cells in the laboratory and re-injecting them back into patients, so-called adoptive T cell therapy.
- Research Head: Alvaro Lladser, PhD
- Research Associates: Vincenzo Borgna, MD, PhD
- Postdoctoral Fellows: Sofía Hidalgo, PhD • Farides Saavedra, PhD • Andrés Hernández-Oliveras, PhD • Diego Figueroa, PhD • Ximena López, PhD
- Doctoral Students: Vincenzo Benedetti • Marco Fraga • Sergio Hernández
- Magister Students: Juan Pablo Vega
- Undergraduate Students: Javiera Reyes • Felipe Ardiles
- Research Assistants: Vicente Saavedra
- Pablo Cáceres (Magister student, graduated in 2019), currently research assistant at Universidad Mayor, Chile.
- Evelyn Menares (PhD student, graduated in 2019), currently postdoctoral fellow at Universidad of Chile, Chile.
- Juan Saavedra (Undergraduate student, graduated in 2019), currently PhD student at Universidad de Chile, Chile.
- Javiera Gómez (Undergraduate student, graduated in 2019).
- Felipe Gálvez (Undergraduate student and PhD student, graduated in 2018), currently postdoctoral fellow at University College London, UK.
- Ernesto López (Undergraduate student and Magister student, graduated in 2018), currently PhD student at University College London, UK.
- Ornella Chovar (Magister student, graduated in 2018), currently research assistant at Fundación Ciencia & Vida, Chile.
- Sebastián Cruz (Undergraduate student and Magister student, graduated in 2017), currently PhD student at University of Melbourne, Australia.
- Nicole Rojas (PhD student, graduated in 2016), currently project executive at FONDEF, ANID, Chile.
- Eduardo Durán (Magister student, graduated in 2016), currently PhD student at Universidad del Desarrollo, Chile.
- Camila Flores (Undergraduate student, graduated in 2016), currently research assistant at Autolus Therapeutics, London, UK.
- Nicole Araya (Undergraduate student, graduated in 2016), currently research assistant at Merken Biotech, Chile.
- Paola Murgas (Postdoctoral fellow 2012-2016), currently group leader at Universidad Mayor, Chile.
- César Oyarce (PhD student, graduated in 2015), currently postdoctoral fellow at University Medical Center Groningen, Netherlands.
- Maarten Ligtenberg (PhD student, graduated in 2015), currently postdoctoral fellow at Netherlands Cancer Institute, Netherlands.
- Nicolás Bustamante (Magister student, graduated in 2014)
- Andrés Herrada (Postdoctoral fellow 2011-2012), currently group leader at Universidad Autónoma, Chile.
- Jonathan Roco (Undergraduate student, graduated in 2012), currently postdoctoral fellow at John Curtin School for Medical Research, Australia.
- Paula González (Undergraduate student, graduated in 2012), currently postdoctoral fellow at John Curtin School for Medical Research, Australia.
- Francisca Hofmann (Magister student, graduated in 2022).
- Pablo Contreras (Undergraduate student, graduated in 2022).
- Brian Sirguiado (Undergraduate student, graduated in 2021).
National Collaborations:
• Dr. Rodrigo Pacheco (Fundación Ciencia & Vida).
• Dr. Manuel Varas (Universidad San Sebastián).
• Dr. Flavio Salazar (Universidad de Chile).
• Dr. Daniela Sauma (Universidad de Chile).
• Dr. Fabiola Osorio (Universidad de Chile).
International Collaborations:
• Dr. Eliane Piaggio (Curie Institute, France).
• Dr. Sergio Quezada (University College London, UK).
• Dr. Rolf Kiessling (Karolinska Institute, Sweden).
• Dr. Andreas Lundqvist (Karolinska Institute, Sweden).
Publications
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)
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)
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)
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)
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)
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
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
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
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
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
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
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
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
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
Medel B, Costoya C, Fernandez D, Pereda C, Lladser A, Sauma D, Pacheco R, Iwawaki T, Salazar-Onfray F, Osorio F. IRE1α Activation in Bone Marrow-Derived Dendritic Cells Modulates Innate Recognition of Melanoma Cells and Favors CD8+ T Cell Priming. Front Immunol. 9:3050. doi: 10.3389/fimmu.2018.03050 (2019) | PDF
Mora JJ, Del Campo M, Villar J, Paolini F, Curzio G, Venuti A, Jara L, Ferreira J, Murgas P, Lladser A, Manubens A, Becker MI. Immunotherapeutic potential of mollusk hemocyanins in combination with human vaccine adjuvants in murine models of oral cancer. J Immunol Res. 2019:7076942. doi: 10.1155/2019/7076942 (2019) | PDF
Prado C, Ugalde V, González H, Figueroa A, López E, Lladser A, Pacheco R. STAT3 Activation in Combination with NF-KappaB Inhibition Induces Tolerogenic Dendritic Cells with High Therapeutic Potential to Attenuate Collagen-Induced Arthritis. J Immunol Res. 2019:1982570. doi: 10.1155/2019/1982570 (2019) | PDF
Arce M, Pinto MP, Galleguillos M, Muñoz C, Lange S, Ramirez C, Erices R, Gonzalez P, Velasquez E, Tempio F, Lopez MN, Salazar-Onfray F, Cautivo K, Kalergis AM, Cruz S, Lladser A, Lobos-González L, Valenzuela G, Olivares N, Sáez C, Koning T, Sánchez FA, Fuenzalida P, Godoy A, Contreras Orellana P, Leyton L, Lugano R, Dimberg A, Quest AFG, Owen GI. Coagulation Factor Xa Promotes Solid Tumor Growth, Experimental Metastasis and Endothelial Cell Activation. Cancers (Basel). 11(8):1103. doi: 10.3390/cancers11081103 (2019) | PDF
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*. Resident memory CD8+ T cells amplify anti-tumor immunity by triggering antigen spreading through dendritic cells. Nature Communications. 10(1):4401. doi: 10.1038/s41467-019-12319-x (2019) | PDF
Lillo P, Núñez O, Castro-Sepúlveda M, Torres-Quintana MA, Lladser Á, Quest AFG, Espinoza C, Llanos P, Wehinger S. Loss of Caveolin-1 Is Associated with a Decrease in Beta Cell Death in Mice on a High Fat Diet. Int J Mol Sci. 23;21(15):5225. doi: 10.3390/ijms21155225 (2020) | PDF
Sanhueza C, Bennett JC, Valenzuela-Valderrama M, Contreras P, Lobos-González L, Campos A, Wehinger S, Lladser Á, Kiessling R, Leyton L, Quest AFG. Caveolin-1-Mediated Tumor Suppression Is Linked to Reduced HIF1α S-Nitrosylation and Transcriptional Activity in Hypoxia. Cancers (Basel). 20;12(9):E2349. doi: 10.3390/cancers12092349 (2020) | PDF
Cáceres-Morgado P, Lladser A. Tumor-Specific CD8+ T-Cell Responses Induced by DNA Vaccination. Methods Mol Biol. 2197:225-239. doi: 10.1007/978-1-0716-0872-2_12 (2021) | PDF
Bourdely P, Vaivode K, Anselmi G, Ramos RN, Missolo Y, Hidalgo S, Tosselo J, Nuñez N, Richer W, Vincent-Salomon A, Saxena A, Wood K, Lladser A, Piaggio E, Helft J, Guermonprez P. Transcriptional and functional analysis of CD1c+ human dendritic cells identifies a CD163+ subset priming CD8+CD103+ T cells. Immunity. 53(2):335-352.e8. doi: 10.1016/j.immuni.2020.06.002. (2020) | PDF
