The additional facet of immunoscore: immunoprofiling as a possible predictive tool for cancer treatment
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EDITORIAL
Open Access
The additional facet of immunoscore: immunoprofiling as a possible predictive tool for cancer treatment Paolo A Ascierto1*, Mariaelena Capone1, Walter J Urba2, Carlo B Bifulco2, Gerardo Botti1, Alessandro Lugli3, Francesco M Marincola4, Gennaro Ciliberto1, Jérôme Galon5,6,7 and Bernard A Fox2,8
Abstract Recent investigations of the tumor microenvironment have shown that many tumors are infiltrated by inflammatory and lymphocytic cells. Increasing evidence suggests that the number, type and location of these tumor-infiltrating lymphocytes in primary tumors has prognostic value, and this has led to the development of an ‘immunoscore. As well as providing useful prognostic information, the immunoscore concept also has the potential to help predict response to treatment, thereby improving decision- making with regard to choice of therapy. This predictive aspect of the tumor microenvironment forms the basis for the concept of immunoprofiling, which can be described as ‘using an individual’s immune system signature (or profile) to predict that patient’s response to therapy’ The immunoprofile of an individual can be genetically determined or tumor-induced (and therefore dynamic). Ipilimumab is the first in a series of immunomodulating antibodies and has been shown to be associated with improved overall survival in patients with advanced melanoma. Other immunotherapies in development include anti-programmed death 1 protein (nivolumab), anti-PD-ligand 1, anti-CD137 (urelumab), and anti-OX40. Biomarkers that can be used as predictive factors for these treatments have not yet been clinically validated. However, there is already evidence that the tumor microenvironment can have a predictive role, with clinical activity of ipilimumab related to high baseline expression of the immune-related genes FoxP3 and indoleamine 2,3dioxygenase and an increase in tumor-infiltrating lymphocytes. These biomarkers could represent the first potential proposal for an immunoprofiling panel in patients for whom anti-CTLA-4 therapy is being considered, although prospective data are required. In conclusion, the evaluation of systemic and local immunological biomarkers could offer useful prognostic information and facilitate clinical decision making. The challenge will be to identify the individual immunoprofile of each patient and the consequent choice of optimal therapy or combination of therapies to be used. Keywords: Tumor microenvironment, Tumor-infiltrating lymphocytes, Immunoprofiling, Immunotherapy, Ipilimumab Recent investigations of the tumour microenvironment (TME) have shown that many tumors are heavily infiltrated by a complex repertoire of inflammatory and lymphoid cells. Immune cells appear as dense infiltrates in the center of the tumoral zone, at the invasive margin of the tumor, and as lymphoid islets adjacent to the tumor. Increasing evidence supports the hypothesis that * Correspondence: [email protected] 1 Melanoma, Cancer Immunotherapy and Innovative Therapy Unit, Istituto Nazionale Tumori Fondaz
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