Dynamics of the antitumor immune response

"Gracias a la microscopía intravital podemos observar directamente a las defensas en acción mientras intentan eliminar a los tumores. De esta forma podemos comprender mejor cómo el sistema inmunitario elimina tumores y porque no lo consigue para así desarrollar nuevas inmunoterapias."

DR. ÁLVARO TEIJEIRA SÁNCHEZ
RESEARCHER. RESEARCH GROUP ON DYNAMICS OF THE ANTITUMOR IMMUNE RESPONSE

Despite the tremendous success that cancer immunotherapy has had in many types of tumors, there are still many patients who do not benefit from these therapies.

Many of the tumors that do not respond to tumor immunotherapy are characterized by poor immune infiltration or because the cells of our defenses that infiltrate them work in favor of the tumor, favoring its progression.

Our group, integrated in the Cancer Center Clínica Universidad de Navarra, has the unique ability to directly observe immune system cells in action using advanced microscopy. We use this technology to understand how immune system cells interact with each other and with tumors, revealing mechanisms by which cancer hijacks the immune system to act in its favor.

Thanks to these observations we can better understand the mechanisms of action of drugs and drugs that modulate the immune response (Immunotherapy) as well as identify new immunosuppressive mechanisms susceptible to therapeutic intervention.

In turn, we are particularly interested in the mechanisms by which tumors attract immune system cells to exploit them in favor of an antitumor immune response.

To this end, we have animal models and close internal and external collaborations that help us to identify relevant problems or new immunotherapies to observe in action under the magnifying glass of our microscopes.

Dr. Álvaro Teijeira Sánchez

GROUP LEADER

   +34 948 194 700
    ateijeiras@unav.es
   Research profile

Oncology research integrated in the
Cancer Center Clinica Universidad de Navarra

Objectives of the Dynamics of the antitumor immune response Group

We use intravital microscopy and other imaging techniques to understand the dynamics of immune responses against the tumor and their interactions both between immune cells and with malignant cells and other stromal components in order to identify new targets and better understand the mechanisms of action of immunotherapy.

To understand the role of neutrophils and extracellular DNA traps in tumor progression.

To investigate the mechanisms that govern the recruitment of immune cells to tumors and to generate new therapies to increase it.

To characterize the tissue-specific immune response to the appearance of early metastases. 

Intravital microscopy

We use advanced microscopy techniques to understand the interaction between our immune system and cancer, as well as the spatial arrangement of immune cells in the tumor microenvironment, which influences the development of responses that can promote or inhibit tumor growth. In recent years, intravital microscopy has revealed a number of previously unknown mechanisms operating in this tumor environment (Teijeira et al Immunity 2020).

The next step is to apply this technique in preclinical studies of immunotherapies to understand how these therapies can modulate, or be modulated by, these dynamic events. This will allow us to uncover some of the secrets underlying their mechanisms of action in vivo.

Lines of research

PI: Álvaro Teijeira

Neutrophils are our body's first line of defense against many bacterial or fungal infections. However, in many patients, cancer is able to hijack the functionality of neutrophils and make them work in its favor. Our group tries to understand in which contexts these extracellular neutrophil traps are formed in cancer and how they are able to induce immunosuppressive effects in the tumor microenvironment.

Objectives:

  • To define the stimuli and conditions under which the release of neutrophil extracellular traps is induced in cancer.
  • To discover the mechanisms by which neutrophil extracellular traps inhibit the antitumor immune response in order to identify new targets for cancer immunotherapy.

PI: Álvaro Teijeira

One of the most important defining characteristics of tumors that do not respond to immunotherapy is the presence of a poor or inadequate immune infiltrate. This project seeks to understand the role of blood vessels in regulating the infiltration of immune system cells into tumors. On the one hand we seek to understand what limitations vessels impose on the immune system to infiltrate tumors and on the other hand we seek novel therapies specifically aimed at maximizing the entry of anti-tumor immune cells into tumors. 

Objectives:

  • To understand the mechanisms that define the interaction of immune system cells with tumor endothelium. 
  • To design new immunotherapies to maximize the appropriate infiltration of tumors by the immune system. 

Scientific activity of the Dynamics of the antitumor immune response research group