title: Emerging Opportunities and Challenges in Cancer Immunotherapy.
abstract: Immunotherapy strategies against cancer are emerging as powerful weapons for treatment of this disease. The success of checkpoint inhibitors against metastatic melanoma and adoptive T-cell therapy with chimeric antigen receptor T cells against B-cell-derived leukemias and lymphomas are only two examples of developments that are changing the paradigms of clinical cancer management. These changes are a result of many years of intense research into complex and interrelated cellular and molecular mechanisms controling immune responses. Promising advances come from the discovery of cancer mutation-encoded neoantigens, improvements in vaccine development, progress in delivery of cellular therapies, and impressive achievements in biotechnology. As a result, radical transformation of cancer treatment is taking place in which conventional cancer treatments are being integrated with immunotherapeutic agents. Many clinical trials are in progress testing potential synergistic effects of treatments combining immunotherapy with other therapies. Much remains to be learned about the selection, delivery, and off-target effects of immunotherapy used alone or in combination. The existence of numerous escape mechanisms from the host immune system that human tumors have evolved still is a barrier to success. Efforts to understand the rules of immune cell dysfunction and of cancer-associated local and systemic immune suppression are providing new insights and fuel the enthusiasm for new therapeutic strategies. In the future, it might be possible to tailor immune therapy for each cancer patient. The use of new immune biomarkers and the ability to assess responses to therapy by noninvasive monitoring promise to improve early cancer diagnosis and prognosis. Personalized immunotherapy based on individual genetic, molecular, and immune profiling is a potentially achievable future goal. The current excitement for immunotherapy is justified in view of many existing opportunities for harnessing the immune system to treat cancer.
authors.affiliation: Department of Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Theresa L
authors.initials: TL
authors.lastname: Whiteside
authors.affiliation: Department of Radiation Oncology, University of Cornell, New York, New York.
authors.forename: Sandra
authors.initials: S
authors.lastname: Demaria
authors.affiliation: Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain. Clinica Universidad de Navarra, Pamplona, Spain.
authors.forename: Maria E
authors.initials: ME
authors.lastname: Rodriguez-Ruiz
authors.affiliation: Department of Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Hassane M
authors.initials: HM
authors.lastname: Zarour
authors.affiliation: Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain. Clinica Universidad de Navarra, Pamplona, Spain. imelero@unav.es.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Melero
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D003131:Combined Modality Therapy; D006801:Humans; D056747:Immunomodulation / Q000187:drug effects; D007167:Immunotherapy; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D059016:Tumor Microenvironment / Q000187:drug effects / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents