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Immunotherapy and predictive immunologic profile: the tip of the iceberg

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Abstract

The interplay between cancer and the immune system has been under investigation for more than a century. Immune checkpoint inhibitors have changed the outcome of several tumors; however, there is a significant percentage of patients presenting resistance to immunotherapy. Besides the action mechanism, it is essential to unravel this complex interplay between host immune system and tumorigenesis to determine an immune profile as a predictive factor to immune checkpoint blockade agents. Tumor expression of programmed death-ligand 1 (PD-L1), tumor mutational burden, or mismatch repair deficiency are recognized predictive biomarkers to immunotherapy but are insufficient to explain the response rates and heterogeneity across tumor sites. Therefore, it is crucial to explore the role of the tumor microenvironment in the diversity and clonality of tumor-infiltrating immune cells since different checkpoint molecules play an influential role in cytotoxic T cell activation. Moreover, cytokines, chemokines, and growth factors regulated by epigenetic factors play a complex part. Peripheral immune cells expressing PD-1/PD-L1 and the biologic roles of soluble immune checkpoint molecules are the subject of new lines of investigation. This article addresses some of the new molecules and mechanisms studied as possible predictive biomarkers to immunotherapy, linked with the concept of immune dynamics monitoring.

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Authors and Affiliations

  1. Medical Oncology Department, Portuguese Oncolology Institute of Coimbra Francisco Gentil, Avenida Bissaya Barreto, 98, 3000-075, Coimbra, Portugal

    Tatiana Cunha Pereira, Fábio Rêgo Salgueiro, Ana Raquel Monteiro, Filipa Macedo, Rita Félix Soares, Isabel Domingues, Paula Jacinto & Gabriela Sousa

  2. Immunology Institute, Faculty of Medicine, University of Coimbra, Coimbra, Portugal

    Paulo Rodrigues-Santos & Jani Sofia Almeida

  3. Laboratory of Immunology and Oncology, Center for Neuroscience and Cell Biology (CNC), University of Coimbra, Coimbra, Portugal

    Paulo Rodrigues-Santos & Jani Sofia Almeida

  4. Center of Investigation in Environment, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, Coimbra, Portugal

    Paulo Rodrigues-Santos & Jani Sofia Almeida

  5. Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, Coimbra, Portugal

    Paulo Rodrigues-Santos & Jani Sofia Almeida

  6. Center for Innovation in Biomedicine and Biotechnology (CIBB), University of Coimbra, Coimbra, Portugal

    Paulo Rodrigues-Santos & Jani Sofia Almeida

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  1. Tatiana Cunha Pereira
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Correspondence to Tatiana Cunha Pereira.

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Cunha Pereira, T., Rodrigues-Santos, P., Almeida, J.S. et al. Immunotherapy and predictive immunologic profile: the tip of the iceberg. Med Oncol 38, 51 (2021). https://doi.org/10.1007/s12032-021-01497-8

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