Immunotherapy against endocrine malignancies: immune checkpoint inhibitors lead the way
- 1Laboratory of Cancer Molecular Genetics, Faculty of Medical Sciences, University of Campinas (FCM-Unicamp), Campinas, São Paulo, Brazil
- 2Liver and Gastrointestinal Transplant Division, Department of Gastroenterology, University of São Paulo, School of Medicine, São Paulo, São Paulo, Brazil
- Correspondence should be addressed to L S Ward; Email: ward{at}fcm.unicamp.br
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Figure 1
Immunological synapse, showing tight contact between a T cell and an antigen-presenting cell. In the lower part of the image, the T-cell interacts with a dendritic cell, and the peptide is presented by MHC and recognized by TCR. In the upper part of the image, the tumor cell performs an analogous presentation of the tumor-associated antigen. When antigen presentation occurs in the context of inhibitory molecules (CTLA-4/B7-1/2 or PD-1/PD-L1), a negative signal is triggered in the cytoplasm of the T-cell. This negative signal leads to the downregulation of effector functions, inhibition of survival, growth and proliferation and stimulation of an exhausted phenotype in T cells. Cancer cells disrupt immune responses by hijacking this mechanism, thereby avoiding tumor destruction and elimination.
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Figure 2
Immunological synapse after the administration of immune checkpoint inhibitors. Immune checkpoint inhibitors are antibodies directed against co-inhibitory molecules. By blocking the interaction between CTLA-4 and B7-1/2 (e.g., ipilimumab) or PD-1 (e.g., nivolumab and pembrolizumab) and PD-L1 (e.g., durvalumab, atezolizumab and avelumab), immune checkpoint inhibitors inhibit the immune response mediated by immune escape mechanisms and encourage the immune system to destroy tumor cells.
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Figure 3
Immune microenvironment in pancreatic adenocarcinoma. Immune cells (e.g., T cells, macrophages, monocytes, mast cells, neutrophils and myeloid-derived suppressor cells) are frequently found in these tumors. Although some effector cells are sparsely observed in the leukocytic infiltrate, pancreatic cancer tissues are markedly infiltrated by immune cells with immunosuppressive functions, from early pre-invasive to advanced overt invasive stages. Additionally, invasive tumors are enriched in myeloid-derived suppressor cells.
- © 2017 Society for Endocrinology
