Preface

Immune checkpoint inhibitors（ICIs）have changed the treatment of a wide range of cancers in the rapidly changing f ield of oncology. These treatments have offered many people fresh hope by utilizing the immune system's capacity to identify and destroy cancer cells while promising long-term life. However，much like any signif icant advancement in medical science， they are not without problems.

Immune checkpoints are regulatory pathways that modulate T-cell responses to presented antigens. In healthy individuals， immune checkpoint proteins mediate self-tolerance and prevent T cells from attacking normal cells indiscriminately. In the process of carcinogenesis， genomic instability may result in multiple gene mutations， and these mutations produce abnormal proteins that can be recognized as“non-self，” i.e.，neoantigens. A hallmark of cancer is evasion of immune surveillance， and malignant cells have“learned” how to use various mechanisms to hide from the immune system， some of which involve immune checkpoints.

In recent years， antibody drugs that bind and inhibit the function of several immune checkpoint proteins［cytotoxic T lymphocyte-associated antigen 4（CTLA-4）， lymphocyte-activation gene-3（LAG3），programmed cell death protein-1（PD-1）， and one of its ligands（PD-L1）］have revolutionized cancer therapy.To date， eleven ICIs have been approved by the US Food and Drug Administration and more outside the US.These are various types of monoclonal antibodies， and the infusion of these biologicals is associated with potential anaphylactoid reactions or infusion-related cytokine release syndrome. Boosting the immune system to treat cancer is a double-edged sword： the enhanced immune activity attacks the cancer cells， but it often leads to autoimmune diseases as well. Immune-related adverse effects（irAEs）arising from ICI therapy vary in incidence and spectrum for the immune checkpoint proteins targeted and the types of malignancy being treated， and combination therapy with different ICIs tends to cause more frequent and more severe irAEs than monotherapy.

The f irst ICI， ipilimumab， was developed at MD Anderson Cancer Center. Being an emergency physician in a comprehensive cancer center， I have been on the front line to diagnose and manage serious irAEs since the very beginning of cancer immunotherapy using ICIs. ICIs are being increasingly used in various combinations for a wide variety of cancer. As new agents targeting new checkpoint proteins and novel combinations of agents come into use， the relative proportions of irAEs seen in treatment-related adverse reactions may shift.

This book is unique in that it is a comprehensive discussion of novel syndromes of oncologic complications（i.e.， irAEs）. irAEs can appear in almost any organ system. They can range from mild and selflimiting to severe and life-threatening. Understanding， diagnosing， and managing these particular problems is crucial for doctors in all specialties as ICIs become a staple in the cancer treatment arsenal.

The complex tango between immunotherapy and its unexpected effects is the subject of this book. We explain the wide range of clinical manifestations， delve into the mechanistic insights of various irAEs， and share our experience in clinical management. Our goal is to empower healthcare professionals to give their patients the best treatment possible.

We made an effort to give the most recent evidence and suggestions possible， drawing on clinical trials，real-world experiences， and expert consensus， as we are aware that the area is continuously evolving and expanding. We also recognize that tackling irAEs requires a multidisciplinary approach. This book offers a comprehensive approach to patient care thanks to contributions from experts in a variety of specialties and domains， including dermatology， cancer， rheumatology， and endocrinology.

We believe this book will serve as a beacon， illuminating the intricacies of irAEs for the aspiring oncologist， the experienced internist， the attentive nurse， the enquiring researcher， and any other stakeholder in the care of cancer patients. Knowledge is our most powerful tool when facing a challenge. Let this book be your reliable companion as we continue to explore the frontier of cancer immunotherapy.

With optimism and enthusiasm，

Yeung Sai-Ching，MD，PhD，FACP

Professor of Medicine

Director of Research

Ashbel Smith Professor

Department of Emergency Medicine

The University of Texas MD Anderson Cancer Center

Houston，Texas，USA

October 2023