Renata Grifantini

This lab is focused on the identification and validation of novel biomarkers for autoimmune diseases and cancer, that could be exploited to improve diagnosis, predict the most probable outcome of the diseases and monitor response to a given therapy. Moreover, we are interested in the selection and characterization on novel molecular targets to the development of innovative therapies. Two of our major current studies are outlined below.

Seronegative rheumatoid arthritis
Chronic inflammatory arthritis, such as rheumatoid arthritis (AR) and related forms (spondyloarthritis, juvenile chronic arthritis) are autoimmune diseases that affect 2% of the general population. They have a chronic course, with different aggressiveness. If not timely diagnosed and handled, they can damage to joint tissues and cause severe disabilities. Diagnosis is based on clinical evidence, imaging data and the recognition of biomarkers, including rheumatoid factor (RF) IgG-IgM-IgA, and anti-IgG citrullinated peptides (ACPA). However, at present there are not validated sensitive biomarkers to estimate treatment efficacy for a given patient. Moreover, a significant fraction of patients is negative for RF or ACPA (seronegative arthritis) making the diagnosis more difficult and delaying the pharmacological treatment. Objective of our study is the identification / validation of biomarkers able to fill the serological gap, to select potential therapeutic targets and offer new insights into the mechanisms underlying this pathology.

Novel targets for cancer immunotherapy
In oncologic patients, effective anti-tumor immune responses are suppressed by immunological pathways (immune checkpoints), cytokines and a subset of tumor infiltrating lymphocytes called T regulatory cells (Treg cells). Immune checkpoints inhibitors (e.g. anti-CTLA4, PD-1/PD-L1 monoclonal antibodies) able to unleash effective anti-tumor immune responses are emerging as breakthrough in the treatment of many cancers. However, approved monoclonal antibodies towards immune checkpoints often cause serious immune-related adverse events (irAEs) likely due to a general depression of the immune system. Although steroids can be used to reduce irAEs, the associated immune suppression can compromise therapy efficacy. We believe that irAEs could be overcome by a selective targeting of tumor-infiltrating T reg cells. Antibodies able to deplete this cell population should de-repress the local immune response in the tumor lesion, while maintaining safe therapeutic profiles.

In continuation with transcriptome studies so far conducted at INGM (Massimiliano Pagani and Sergio Abrignani), our group is interested in exploiting a gene signature associated to tumor infiltrating Tregs (De Simone M. et al., Immunity 2016) to select novel immune-modulators suitable for the generation of therapeutic monoclonal antibodies.