title: Near future of tumor immunology: Anticipating resistance mechanisms to immunotherapies, a big challenge for clinical trials.
abstract: The success of immunotherapies brings hope for the future of cancer treatment. Even so, we are faced with a new challenge, that of understanding which patients will respond initially and, possibly, develop resistance. The examination of the immune profile, especially approaches related to the immunoscore, may foretell which tumors will have a positive initial response. Ideally, the mutation load would also be analyzed, helping to reveal tumor associated antigens that are predictive of an effective cytolytic attack. However, the response may be hindered by changes induced in the tumor and its microenvironment during treatment, perhaps stemming from the therapy itself. To monitor such alterations, we suggest that minimally invasive approaches should be explored, such as the analysis of circulating tumor DNA. When testing new drugs, the data collected from each patient would initially represent an N of 1 clinical trial that could then be deposited in large databases and mined retrospectively for trends and correlations between genetic alterations and response to therapy. We expect that the investment in personalized approaches that couple molecular analysis during clinical trials will yield critical data that, in the future, may be used to predict the outcome of novel immunotherapies.
authors.affiliation: a Viral Vector Laboratory, Center for Translational Investigation in Oncology , Cancer Institute of Sao Paulo/LIM 24, University of São Paulo School of Medicine , São Paulo , Brazil.
authors.forename: João Paulo Portela
authors.initials: JPP
authors.lastname: Catani
authors.affiliation: b Cancer Institute of Sao Paulo , University of São Paulo School of Medicine , São Paulo , Brazil.
authors.forename: Rachel P
authors.initials: RP
authors.lastname: Riechelmann
authors.affiliation: c Laboratory of Cell and Molecular Biology, Departament of Immunology , Biomedical Sciences Institute, University of São Paulo , São Paulo , Brazil.
authors.forename: Sandy
authors.initials: S
authors.lastname: Adjemian
authors.affiliation: a Viral Vector Laboratory, Center for Translational Investigation in Oncology , Cancer Institute of Sao Paulo/LIM 24, University of São Paulo School of Medicine , São Paulo , Brazil.
authors.forename: Bryan E
authors.initials: BE
authors.lastname: Strauss
mesh_terms: D002986:Clinical Trials as Topic; D004247:DNA / Q000097:blood; D018816:Genes, cdc; D006801:Humans; D007167:Immunotherapy / Q000009:adverse effects / Q000379:methods / Q000639:trends*; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000276:immunology* / Q000628:therapy*; D057285:Precision Medicine; D059016:Tumor Microenvironment
chemical_list: D004247:DNA
keywords: cancer; checkpoint blockade; circulating tumor DNA; immunoscore; personalized medicine