TY - JOUR
T1 - Autoimmunity, checkpoint inhibitor therapy and immune-related adverse events
T2 - A review
AU - Khan, Shaheen
AU - Gerber, David E.
N1 - Funding Information:
The authors thank Ms. Helen Mayo, MLS, from the UT Southwestern Medical Library, for assistance with literature searches. Funded by an American Cancer Society-Melanoma Research Alliance Team Award (MRAT-18-114-01-LIB; to DEG), a National Cancer Institute Midcareer Investigator Award in Patient-Oriented Research (K24 CA201543-01; to DEG), and a V Foundation Robin Roberts Cancer Survivorship Award (DT2019-007; to DEG), and a Melanoma Research Alliance-Society for Immunotherapy of Cancer Young Investigator Award in Immune-related Adverse Events (Award number: 619351; to SK).
Publisher Copyright:
© 2019 Elsevier Ltd
PY - 2020/8
Y1 - 2020/8
N2 - Immune checkpoint inhibitors have emerged as a remarkable treatment option for diverse cancer types. However, a significant number of patients on checkpoint inhibitors develop immune-related adverse events (irAEs) affecting a wide variety of organs. These events, which may reflect enhanced T cell activation, are unpredictable, heterogeneous, and in some instances permanent or life-threatening. It is not clear whether these toxicities are distinct from conventional autoimmune diseases or whether the manifestation of irAEs is associated with therapeutic efficacy. Studies across the spectrum of basic, preclinical and clinical research deciphering the role of genetics, epigenetics, gut microbiota and underlying immune status of patients who develop irAEs are required to gain a deeper mechanistic understanding. Insights gained from such studies will facilitate identification of biomarkers for optimal treatment and clinical management of patients. In this Review, we provide basic and clinical understanding of immune checkpoint inhibitors and irAEs. We discuss the connection between immune system, autoimmunity and cancer; immune checkpoint inhibitors and associated autoimmune toxicities; insights into potential underlying mechanisms of irAEs; impact of autoimmune diagnosis on cancer outcome; and management of irAEs.
AB - Immune checkpoint inhibitors have emerged as a remarkable treatment option for diverse cancer types. However, a significant number of patients on checkpoint inhibitors develop immune-related adverse events (irAEs) affecting a wide variety of organs. These events, which may reflect enhanced T cell activation, are unpredictable, heterogeneous, and in some instances permanent or life-threatening. It is not clear whether these toxicities are distinct from conventional autoimmune diseases or whether the manifestation of irAEs is associated with therapeutic efficacy. Studies across the spectrum of basic, preclinical and clinical research deciphering the role of genetics, epigenetics, gut microbiota and underlying immune status of patients who develop irAEs are required to gain a deeper mechanistic understanding. Insights gained from such studies will facilitate identification of biomarkers for optimal treatment and clinical management of patients. In this Review, we provide basic and clinical understanding of immune checkpoint inhibitors and irAEs. We discuss the connection between immune system, autoimmunity and cancer; immune checkpoint inhibitors and associated autoimmune toxicities; insights into potential underlying mechanisms of irAEs; impact of autoimmune diagnosis on cancer outcome; and management of irAEs.
KW - Autoimmunity
KW - Immune checkpoint inhibitors
KW - Immunotherapy
KW - Toxicity and irAEs
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U2 - 10.1016/j.semcancer.2019.06.012
DO - 10.1016/j.semcancer.2019.06.012
M3 - Review article
C2 - 31330185
AN - SCOPUS:85069837556
SN - 1044-579X
VL - 64
SP - 93
EP - 101
JO - Seminars in Cancer Biology
JF - Seminars in Cancer Biology
ER -