IDENTIFICATION OF NEW BIOLOGICAL PROGNOSTIC FACTORS IN TUMOURS OF HAEMATOPOIETIC AND LYMPHOID TISSUES: the research aims at identifying biological
prognostic factors, determined at diagnosis, able to select
patients at higher risk of disease progression and chemoresistance
and therefore candidates for intensification of therapy or a targeted therapy.
CHARACTERIZATION OF TUMOR MICROENVIRONMENT. The development and spread of a tumor are the result not only of intrinsic events of the malignant clone, such as oncogenes activation or inactivation of oncosoppressive genes, but also from the ability of the latter to induce a state of immunosuppression in which neoplastic cells are not recognized and destroyed by the immune system (cancer-immunoediting). This phenomenon involves the reprogramming of the immune system by causing a "switch" from an effective anticancer response to a chronic inflammatory state that facilitates neoplastic progression. These mechanisms of escape from immune surveillance are established through the interaction of the tumor with the microenvironment (ME) consisting of leukocytes, accessory cells, stromal cells, extracellular matrix, and involves the production and secretion of numerous cytokines, interleukins and growth factors . A key role in the immuno-evasion process is played by immune-checkpoints, such as PD-1 and PDL1, against which antibodies have been developed, that alone or in combination are modifying the current therapeutic standards both of solid and hematologic neoplasms. The efficacy of these agents seems to be related to the expression of PD-L1 by tumor cells detected by immunohistochemistry, however, a significant group of patients does not respond to IPCIs even in high levels of PD-L1 whereas in other cases therapy is also successful in the absence of PD-L1 on neoplastic cells. The real mechanism of action of this new class of immunotherapeutic drugs is not entirely known, as they target not only neoplastic cells but also MA.The aim of the research, by applying new molecular tools, is to extensively characterize the MA populations of solid and haematological tumors, to understand the interaction between tumor and immune system and to identify patients that should be treated with the new immunotherapeutic agents.
