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Dr Asis Palazón

Dr Asis Palazón

Cancer Immunology

Cancer Immunotherapy

Lymphocyte metabolism

Response to Hypoxia


Research Interests

My research is focused on cancer immunology and immunotherapy. The tumor microenvironment determines many of the hallmarks of cancer. Stromal components and malignant cells dialogue and mutually change their functional responses. Tumor infiltrating lymphocytes (TILs) are a prominent feature of solid tumors, whose presence has been correlated with a better survival outcome in various malignant diseases. However TILs are severely restrained in their ability to tackle tumors as a result of multifactorial immunosuppressive mechanisms. I am working on the hypothesis that low levels of oxygen availability in solid tumors induce profound changes on the adaptative immune response mediated by HIF-1α and HIF-2α transcription factors. New achievements in this field will enable a more rational design of anti-tumor immunotherapies and may help not only to explain disease recurrence, but also to identify potential targets for therapeutic interventions.

Keywords

cytotoxicity ; immunohistochemistry ; co-stimulation ; monocytes ; macrophages ; adhesion molecules ; monoclonal antibodies ; adoptive cell therapy ; co-stimulatory molecules ; T cells ; tumor microenvironment ; cell culture ; cytotoxic T cells (CTL) ; hypoxia ; fluorescence microscopy ; confocal microscopy ; antibody engineering ; FACS ; endothelial cells ; adaptive immunity

Topics

  • therapy
  • immunotherapy
  • cancer

Key Publications

Morales-Kastresana A, Sanmamed MF, Rodriguez I, Palazon A, Martinez-Forero I, Labiano S, Hervas-Stubbs S, Sangro B, Ochoa C, Rouzaut A, Azpilikueta A, Bolaños E, Jure-Kunkel M, Gütgemann I, Melero I. Combined immunostimulatory monoclonal antibodies extend survival in an aggressive transgenic hepatocellular carcinoma mouse model.
Clin Cancer Res. 2013 Nov 15;19(22):6151-62.

Martinez-Forero I, Azpilikueta A, Bolaños-Mateo E, Nistal-Villan E, Palazon A, Teijeira A, Perez-Chacon G, Morales-Kastresana A, Murillo O, Jure-Kunkel M, Zapata JM, Melero I. T cell costimulation with anti-CD137 monoclonal antibodies is mediated by K63-polyubiquitin-dependent signals from endosomes.
J Immunol. 2013 Jun 15;190(12):6694-706. 

Ochoa MC, Fioravanti J, Duitman EH, Medina-Echeverz J, Palazon A, Arina A, Dubrot J, Alfaro C, Morales-Kastresana A, Murillo O, Hervas-Stubbs S, Prieto J, Berraondo P, Melero I. Liver gene transfer of interkeukin-15 constructs that become part of circulating high density lipoproteins for immunotherapy.
PLoS One. 2012;7(12):e52370. d

Morales-Kastresana A, Catalán E, Hervás-Stubbs S, Palazón A, Azpilikueta A, Bolaños E, Anel A, Pardo J, Melero I. Essential complicity of perforin-granzyme and FAS-L mechanisms to achieve tumor rejection following treatment with anti-CD137 mAb. J Immunother Cancer. 2013 May 29;1:3. 

Bustos M, Dubrot J, Martinez-Anso E, Larequi E, Castaño D, Palazon A, Belza I, Sanmamed MF, Perez-Gracia JL, Ortiz de Solorzano C, Alfaro C, Melero I. Cardiotrophin-1 determines liver engraftment of syngenic colon carcinoma cells through an immune system-mediated mechanism. Oncoimmunology. 2012 Dec 1;1(9):1527-1536.

Palazón A, Martínez-Forero I, Teijeira A, Morales-Kastresana A, Alfaro C, Sanmamed MF, Perez-Gracia JL, Peñuelas I, Hervás-Stubbs S, Rouzaut A, de Landázuri MO, Jure-Kunkel M, Aragonés J, Melero I. The HIF-1α Hypoxia Response in Tumor-Infiltrating T Lymphocytes Induces Functional CD137 (4–1BB) for Immunotherapy. Cancer Discovery. 2012 Jul;2(7):608–23.

Palazón A, Aragonés J, Morales-Kastresana A, de Landázuri MO, Melero I. Molecular pathways: hypoxia response in immune cells fighting or promoting cancer. Clinical Cancer Research. 2012 Mar 1;18(5):1207–13

Palazón A, Teijeira A, Martínez-Forero I, Hervás-Stubbs S, Roncal C, Peñuelas I, Dubrot J, Morales-Kastresana A, Pérez-Gracia JL, Ochoa MC, Ochoa-Callejero L, Martínez A, Luque A, Dinchuk J, Rouzaut A, Jure-Kunkel M, Melero I. Agonist anti-CD137 mAb act on tumor endothelial cells to enhance recruitment of activated T lymphocytes. Cancer Research. 2011 Feb 1;71(3):801–11