Cancer Immunotherapy                     

Principal Investigator

Staff

Research topic

The mission of the Cancer Immunotherapy Laboratory is to explore innovative preclinical and translational immunotherapy strategies for the treatment of solid tumors resistant to conventional therapies. The main research lines include:
– Translational development of novel cellular immunotherapy approaches, including TIL and CAR-engineered killer lymphocytes, in clinical oncology contexts characterized by poor responsiveness to standard treatments. Particular attention is given to the targeting of the cancer stem cell (CSC) compartment, recognized as a driver of therapeutic resistance and disease relapse.
– Immunological profiling of patients undergoing immunotherapy or conventional treatments, aimed at identifying biomarkers of response and resistance.
The laboratory’s activity mainly focuses on melanoma, sarcomas, breast and ovarian cancers, while maintaining a broader translational perspective applicable to multiple solid tumor types.

Background

Cellular immunotherapy represents one of the most promising frontiers in oncology, spanning from the clinical application of tumor-infiltrating lymphocytes (TIL) to next-generation platforms based on engineered receptors—such as T-cell receptor (TCR) or chimeric antigen receptor (CAR)—for advanced malignancies. In metastatic melanoma, TIL therapy is entering clinical use, while CAR-T cells have revolutionized the treatment of hematologic cancers. However, the translation of these approaches to solid tumors remains challenging due to antigenic heterogeneity, immunosuppressive tumor microenvironments, and physical or metabolic barriers that limit effector-cell infiltration and persistence. Despite progress achieved with molecular-targeted agents and immune checkpoint inhibitors, a significant proportion of patients with advanced solid tumors still experiences early relapse or primary resistance, emphasizing the urgent need for innovative immunotherapeutic strategies.

Research achievements

The laboratory’s research builds upon a strong translational background, originating from early work in hematopoietic cell transplantation and progressively evolving toward adoptive immunotherapy for solid tumors. Key scientific contributions include:
1. The identification of cytokine-induced killer (CIK) lymphocytes as a valuable platform for CAR-engineering strategies against solid tumors, demonstrating their potential in difficult clinical settings such as advanced sarcomas and highlighting their favorable biological features compared with conventional CAR-T cells. This platform has also been extended to hematopoietic transplantation contexts.
2. The discovery of a novel, lymphocyte-independent antitumor effect of anti-PD-1 antibodies on a subset of pro-tumorigenic, stem-like tumor cells (in melanoma and lung cancer) expressing the         PD-1      receptor.
3. The demonstration of the preclinical efficacy of CIK and CAR-CIK lymphocytes against chemoresistant melanoma and sarcoma cancer stem cells.
4. The exploration of antitumor activity and alloreactivity across different CIK subpopulations, including cross-HLA barrier settings.

Conclusions and perspectives

Immunotherapy is emerging as an expanding reality in modern oncology, supported by major translational research efforts. Ongoing and future directions include the development of innovative and patient-tailored preclinical models to better dissect the biological mechanisms underlying tumor response and resistance to immunotherapy, providing a rational foundation for the clinical translation of novel therapeutic approaches against solid tumors refractory to standard treatments.

Publications

At this link, you can find all the scientific publications of the Principal Investigator.