UOSD IMMUNOLOGY AND IMMUNOTHERAPY
Head: Paola Nisticò, MD
The group activity obtained results on the role that the isoforms of the actin regulator hMENA may have in shaping NSCLC microenvironment by regulating the dialogue among tumor, fibroblasts and immune cells. We have demonstrated that hMENA and its isoforms contributes to cancer progression by regulating tumor cell-autonomous signalling, including:
1) AXL; TGFβ/SMAD and IFN type I pathways with PD-L1 up-regulation related to the absence of hMENA11a isoform. In parallel, hMENA/hMENADv6 isoforms identify a subtype of pro-invasive immunosuppressive CAFs. hMENA isoforms from both tumor cells and CAFs impact ECM composition and quality and localization of immune cell in the tumor site. Studies are ongoing to evaluate hMENA derived signatures as theranostic biomarker in NSCLC patients treated with immune checkpoint inhibitors. We have identified significant modulation of immune cell subsets in periphery with respect to distal and tumoral tissue in NSCLC patients by multicolour flow cytometry. An in depth immune-monitoring in prostate cancer patients undergoing curative radiotherapy RT revealed important modification of immune cell frequency and quality, indicating the role of novel targets to be used in combined radio/immunotherapeutic clinical trials.
Paola Nisticò as National coordinator of the WG Immunotherapy of Alleanza Contro il Cancro contributes through an integrated experimental and clinical work in different network projects.
We aim to develop innovative therapeutic strategies for targeting TME components. To this end, we have identified TME-related genes as putative targets for chimeric antigen receptor-modified T cells (CAR-T) and bispecific T-cell engagers (BiTE). Moreover, we are assessing whether treatment with oncolytic viruses can promote T cell trafficking into “cold” solid tumors. Moreover, we characterized a clinical grade product obtained by emulsification of adipose tissue-derived stromal vascular fraction, used in regenerative medicine clinical studies in virtue of its immunosuppressive, immunomodulatory, and pro-angiogenic potentials.
In cooperation with the HPV Unit we participate in programs of cancer prevention on HPV vaccination for males and, recently, we started an International clinical trial on this issue as Italian Coordinator Centre. Patients were enrolled and three years follow-up taking place. We achieved new insight the therapy of HPV-associated cancer. The study in collaboration with University of California, identified a novel mechanism of resistance to anti-PD-1/PD-L1 immunotherapy mediated by HPV16 E5 oncoprotein, which can be exploited using the HPV E5 inhibitor rimantadine to improve outcomes for head and neck cancer patients. Exploring the role of HPV in non-genital cancers, we evidenced that presence of persistent infection by beta papillomavirus type 15 might influence the biological fate of patient with a rare hereditary disease, Inontinentia Pigmenti (IP) by altering NF-κB activation and apoptosis in IKKγ mutated cells, favouring their survival and possibly the development of tumors in the late stage of disease. The platform for the production of DNA therapeutic vaccines has been improved by exploring adjuvating activity of natural compounds. Finally, our mouse model of oral cancer AT-84 was challenged with oncolytic viruses to improve CAR –T cell therapy in solid tumours.