Elucidating the networks of immune stromal connections by Perturbation of Immunity in Cancer - towards developing novel therapeutic strategies | EPIC | Proyecto | Ficha informativa | HORIZON | CORDIS

Descripción del proyecto

Dilucidar las redes de interacciones estromales inmunitarias en el microentorno tumoral

La inmunoterapia beneficia a pocos enfermos de cáncer. Incluso en esos casos, los mecanismos de evasión tumoral modifican los tratamientos, no solo en las células tumorales, sino también en el compartimento estromal del microambiente tumoral, a menudo descartado como posible diana de intervención. Por tanto, es fundamental conocer las interacciones entre el sistema inmunitario y los tumores para desarrollar nuevos tratamientos. En el proyecto EPIC, financiado por el Consejo Europeo de Investigación, se examinarán en detalle las interacciones entre células inmunitarias y células estromales en el microentorno tumoral, identificando las funciones y rutas de cada elemento celular activo, incluidas las interacciones multinivel que se producen antes y después del tratamiento. A continuación, se probarán y validarán «in vivo» posibles sustancias de interés médico para una terapia combinada racional dirigida. Los resultados proporcionarán un marco para comprender mejor la dinámica de la inmunidad tumoral, lo cual dará lugar a nuevas estrategias terapéuticas.

Objetivo

Immune cells monitor and eliminate cancer cells, and thus keep tumors in check along the lifespan of an organism. However, tumors have evolved various mechanisms to avoid immune surveillance. Therefore, understanding these mechanisms and interfering with them to facilitate immune cell eradication of tumor cells is the focus of many successful immunotherapies. However, the efficacy of immunotherapy is limited to only a small fraction of patients and only certain types of cancers. Therefore, it is crucial to understand the immune-tumor interactions to develop new treatments. Moreover, tumor evasion mechanisms interfere with such treatments, as compensatory programs ensue soon after therapeutic intervention. These compensatory programs are not limited to tumor cells, but also occur in the stromal compartment of the tumor microenvironment (TME), which provides indispensable support to the tumor, and is often overlooked as potential target for intervention. Here we aim to gain a fundamental understanding of all cellular networks within the TME, to elucidate the roles and programs carried out by each cellular element participating in the complex, multilevel interactions that occur before therapeutic intervention and afterward.
Toward this goal, we will map the entire spectrum of immune and stromal cell interactions in the TME. We will identify negative- and positive-tumor-regulator dependent programs, primary and compensatory, unique and shared-across pathogenic conditions, and cell-intrinsic and extrinsic programs (Aim 1). Additionally, we aim to identify conserved mouse and human pathways using a parallel mouse and human tumor slice culture system (Aim 2). Based on Aims 1 and 2, we will test and validate new candidates for targeted rational combination therapy in-vivo (Aim 3). Our findings will lay the foundations for a fundamental understanding of tumor immunity dynamics in the TME and create a paradigm shift in immunotherapy