MASCC 2020 recommendations for the management of immune-related adverse events of patients undergoing treatment with imm
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EDITORIAL
MASCC 2020 recommendations for the management of immune-related adverse events of patients undergoing treatment with immune checkpoint inhibitors Bernardo L. Rapoport 1,2 & Ronald Anderson 1 & Tim Cooksley 3,4 & Douglas B. Johnson 5
# Springer-Verlag GmbH Germany, part of Springer Nature 2020
Oncoimmunotherapy with immune checkpoint inhibitor– targeted antibodies has developed as the most significant advance in the management of cancer in recent years [1]. The concept that the immune system was unsuccessful in protecting humans against the development of cancer has changed over the last decade. Checkpoint molecules are inhibitory (PD-1, PDL-1, CTLA-4, TIM-3, LAG-3, BTLA, and HEVM) and stimulatory (CD27, CD40, OX40, GITR, ICOS, and CD137) co-receptors expressed mostly by T cells, but also by other immune cells including antigen-presenting dendritic cells. The basic function of these inhibitory co-receptors is to negatively regulate T cell activation, which is critical in the maintenance of peripheral self-tolerance. The co-inhibitory receptor ligands for these immune checkpoint molecules are, however, also significantly upregulated in various types of cancers, resulting in evasion of anticancer immunity.
* Bernardo L. Rapoport [email protected] Ronald Anderson [email protected] Tim Cooksley [email protected] Douglas B. Johnson [email protected] 1
Department of Immunology, Faculty of Health Sciences, University of Pretoria, PO Box 667, Pretoria 0001, South Africa
2
The Medical Oncology Centre of Rosebank, 129 Oxford Road, Saxonwold, Johannesburg 2196, South Africa
3
Manchester University Foundation Trust, Manchester, UK
4
The Christie, University of Manchester, Manchester, UK
5
Department of Medicine, Vanderbilt University Medical Center and Vanderbilt Ingram Cancer Center, Nashville, TN, USA
Recent advances in immunotherapy include the discovery of the inhibitory immune checkpoint molecules, programmed cell death protein 1 (PD-1), and cytotoxic T lymphocyte–associated antigen 4 (CTLA-4), discovered by Tasuku Honjo and James P. Allison in 1992 and 1996, respectively [2, 3]. In acknowledgment of this pioneering research, these scientists received the 2018 Nobel Prize for Physiology and Medicine. The significant and often durable clinical responses seen with monoclonal antibodies targeting CTLA-4 and PD-1 have resulted in new standards of care in a variety of malignant diseases [1–4], following FDA approval of checkpoint inhibitors that included pembrolizumab [5], nivolumab [6], cemiplimab [7], atezolizumab [8], durvalumab [9], and avelumab [10]. These agents are approved for several indications including melanoma, lung cancer (small and non-small cell types), bladder cancer, renal cell carcinoma, and Hodgkin’s disease [5–10]. Other co-inhibitory molecules under clinical evaluation include T cell immunoglobulin and mucin domain–containing molecule-3 (TIM-3) [11], lymphocyte activation gene-3 (LAG-3) [12], V domain Ig– containing suppressor of T cell activation (VISTA)
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