"Immunotherapeutic approaches to lymphomas: harnessing the mechanisms of the immune system to tackle them"

Abstract

Lymphomas represent a heterogeneous group of hematologic malignancies and are divided in 2 broad groups: Hodgkin and non-Hodgkin lymphomas. Hodgkin lymphomas are characterized by the presence of the giant, multicore Reed-Sternberg cells, which are derived from B lymphocytes. On the contrary, non-Hodgkin lymphomas arise from two distinct lymphocyte types, B or T lymphocytes at various stages of differentiation. Although the first theories about cancer immunotherapy have been proposed since the late 1800s, only recently immunotherapeutic drugs for cancer have been translated into the clinic.

Immunotherapy either alone or in combination with chemotherapy has improved the survival rate of many patients with relapsed or refractory lymphoma. Immunotherapeutic drugs exert their pharmacologic effects via variable routes. Based on their mechanism of action they are divided into different groups. The ones that are analysed in this master thesis are the following: “naked” monoclonal antibodies, conjugated monoclonal antibodies, immune checkpoint inhibitors and CAR T-cell therapies. The immunotherapeutic approach differs between Hodgkin and non-Hodgkin lymphomas and also depends on the stage of the disease. For instance, the immune checkpoint inhibitors constitute a therapeutic option only for Hodgkin lymphoma, but not for the non-Hodgkin lymphoma because of the different histopathology of each disease. Furthermore, the administration of these drugs usually entails severe adverse events and for this reason their administration must take place under certain circumstances and several precaution measures must be taken.

Consequently, immunotherapy has demonstrated positive clinical results regarding the treatment of lymphoma. However, there is some variability regarding the magnitude and the duration of response, which depends on a lot of factors such as the tumour microenvironment, the heterogeneity in tumor biology and host-related factors. For this reason, the need for predictive biomarkers of response is critical.

KOLOVOU Aliki