Multidisciplinary Clinical Approach to Cancer Patients with Immune-Related Adverse Events Induced by Checkpoint Inhibitors

Londoño, María-Carlota; Reig, María

doi:10.3390/cancers12113446

Cited by 22 publications

(22 citation statements)

References 114 publications

(146 reference statements)

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“…have emerged. 182 However, it is not clear which cancer patients who use PD-1/PD-L1 blockers have potential side effects. Many tumors have a background of chronic inflammatory diseases, such as chronic hepatitis, pneumonia, and enteritis.…”

Section: Discussionmentioning

confidence: 99%

Epigenetic Inheritance From Normal Origin Cells Can Determine the Aggressive Biology of Tumor-Initiating Cells and Tumor Heterogeneity

Ji-liang

Zhao

et al. 2022

Cancer Control

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The acquisition of genetic- and epigenetic-abnormalities during transformation has been recognized as the two fundamental factors that lead to tumorigenesis and determine the aggressive biology of tumor cells. However, there is a regularity that tumors derived from less-differentiated normal origin cells (NOCs) usually have a higher risk of vascular involvement, lymphatic and distant metastasis, which can be observed in both lymphohematopoietic malignancies and somatic cancers. Obviously, the hypothesis of genetic- and epigenetic-abnormalities is not sufficient to explain how the linear relationship between the cellular origin and the biological behavior of tumors is formed, because the cell origin of tumor is an independent factor related to tumor biology. In a given system, tumors can originate from multiple cell types, and tumor-initiating cells (TICs) can be mapped to different differentiation hierarchies of normal stem cells, suggesting that the heterogeneity of the origin of TICs is not completely chaotic. TIC’s epigenome includes not only genetic- and epigenetic-abnormalities, but also established epigenetic status of genes inherited from NOCs. In reviewing previous studies, we found much evidence supporting that the status of many tumor-related “epigenetic abnormalities” in TICs is consistent with that of the corresponding NOC of the same differentiation hierarchy, suggesting that they may not be true epigenetic abnormalities. So, we speculate that the established statuses of genes that control NOC’s migration, adhesion and colonization capabilities, cell-cycle quiescence, expression of drug transporters, induction of mesenchymal formation, overexpression of telomerase, and preference for glycolysis can be inherited to TICs through epigenetic memory and be manifested as their aggressive biology. TICs of different origins can maintain different degrees of innate stemness from NOC, which may explain why malignancies with stem cell phenotypes are usually more aggressive.

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Section: Discussionmentioning

confidence: 99%

Epigenetic Inheritance From Normal Origin Cells Can Determine the Aggressive Biology of Tumor-Initiating Cells and Tumor Heterogeneity

Ji-liang

Zhao

et al. 2022

Cancer Control

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“…In future studies, rheumatic irAEs could be integrated into the grading system of non-irAEs induced by ICIs to improve management and facilitate decisions regarding decreasing ICIs and discontinuing therapy. Investigation of potential long-term benefits to patients requires more multi-center, large-scale prospective studies ( 92 ).…”

Section: Management and Remedy Strategies For Rheumatic Iraesmentioning

confidence: 99%

Rheumatic Manifestations and Diseases From Immune Checkpoint Inhibitors in Cancer Immunotherapy

Shen

Chen

et al. 2021

Front. Med.

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Immune checkpoint inhibitors (ICIs), which can enhance antitumor immunity and inhibit cancer growth, have revolutionized the treatment of multiple cancers and dramatically decreased mortality. However, treatment with ICIs is directly associated with immune-related adverse events (irAEs) because of inflammation in off-target organs and autoimmunity resulting from non-specific immune activation. These irAEs can cause rheumatic diseases and manifestations such as inflammatory arthritis, polymyalgia rheumatica, myositis, vasculitis, Sicca and Sjogen's syndrome, and systemic lupus erythematosus. Early diagnosis and treatment of these adverse events will improve outcomes and quality of life for cancer patients. The treatment of rheumatic diseases induced by ICIs requires multidisciplinary cooperation among physicians. Furthermore, the underlying mechanisms are not fully understood and it is difficult to predict and evaluate these side effects precisely. In this review, we summarize available studies and findings about rheumatic irAEs, focusing mainly on the clinical manifestations, epidemiology, possible mechanisms, and guiding principles for treating these irAEs.

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“…In severe cases, prompt hospital admission and emergency dermatology consultation are needed, since these conditions may become fatal if not diagnosed in a timely manner and treated appropriately with high-dose glucocorticoids. [7][8][9]11,12,20 Endocrinological irARs…”

Section: Cardiovascular Iraesmentioning

confidence: 99%

“…In severe cases, systemic corticosteroids and immunosuppressive agents must be used. [7][8][9]11,12 Pulmonary irAEs…”

Section: Hematological Iraesmentioning

confidence: 99%

Management of immune‐related adverse events in anti‐PD‐1‐treated patients with advanced cutaneous squamous cell carcinoma

Gambichler

Scheel

Reuther

et al. 2021

Acad Dermatol Venereol

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Immune checkpoint inhibitors (ICI) have shown very promising results in the management of patients with inoperable or metastatic cutaneous squamous cell carcinoma (cSCC). However, ICI can cause a range of immune‐related adverse events (irAEs) affecting a multitude of organs including skin, gastrointestinal tract, endocrine system, heart, lung, kidneys and the nervous system. In principle, clinical management irAEs does not change significantly with respect to the kind of cancer treated with ICI. However, advanced cSCC typically occurs in a clinically challenging patient population typically presenting with advanced age and/or significant comorbidities such as immunosuppression due to haematological malignancies and their respective treatment. Moreover, many patients with advanced cSCC are organ transplant patients taking immunosuppressants. As a consequence use of ICI per se and management of ICI‐induced irAEs generates more complexity and difficulties in patients with cSCC compared to other entities. Here, we provide a brief review on the management of anti‐programmed cell death protein 1‐induced irAEs in patients with cSCC focusing on the characteristic clinical challenges present in this population.

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Multidisciplinary Clinical Approach to Cancer Patients with Immune-Related Adverse Events Induced by Checkpoint Inhibitors

Cited by 22 publications

References 114 publications

Epigenetic Inheritance From Normal Origin Cells Can Determine the Aggressive Biology of Tumor-Initiating Cells and Tumor Heterogeneity

Epigenetic Inheritance From Normal Origin Cells Can Determine the Aggressive Biology of Tumor-Initiating Cells and Tumor Heterogeneity

Rheumatic Manifestations and Diseases From Immune Checkpoint Inhibitors in Cancer Immunotherapy

Management of immune‐related adverse events in anti‐PD‐1‐treated patients with advanced cutaneous squamous cell carcinoma

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