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Cancers
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Immune-Related Adverse Events in Cancer Immunotherapy
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Immune-Related Adverse Events in Cancer Immunotherapy

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Immunology and Immunotherapy".

Deadline for manuscript submissions: 15 November 2025 | Viewed by 5253

Special Issue Editors

Dr. Kate Young

E-Mail Website
Guest Editor
The Royal Marsden NHS Foundation Trust, Royal Marsden Hospital, London, UK
Interests: medical oncology; immune checkpoint inhibitor toxicities; immunotherapy
Dr. Anna Olsson-Brown

E-Mail Website
Guest Editor
Immunotherapy Team, The Clatterbridge Cancer Centre, Liverpool, UK
Interests: medical oncology; immune checkpoint inhibitor toxicities; immunotherapy

Special Issue Information

Dear Colleagues,

Over the last decade, immunotherapy treatments, particularly immune checkpoint inhibitors, have brought about a paradigm shift in the treatment of multiple solid tumors. These drugs are now used in many settings, from neoadjuvant through to advanced disease, across a wide variety of tumor types and in combination with other systemic anti-cancer therapies, including chemotherapy and tyrosine kinase inhibitors. While these checkpoint inhibitor drugs have revolutionized outcomes for some patients, understanding and treating their attendant side effects, or immune-related adverse events (irAEs), have provided new challenges for the oncology community. While we now know more about the spectrum of irAEs expected with ICIs, less is known about their long-term impact, how best to predict who may suffer from irAEs, how best to capture data on irAEs in clinical trials and in the real world, the mechanisms underlying the different irAEs, how best to treat them, particularly in steroid refractory cases or rarer irAEs, and how to educate our patients and the wider medical community about these very different side effects. Less is still known about the adverse events associated with some of the newer immunotherapies or combination treatments.

This Special Issue ‘Immune-Related Adverse Events in Cancer Immunotherapy’ aims to focus on these topics and more. In this Special Issue, original research articles and reviews are welcome.

We look forward to receiving your contributions.

Dr. Kate Young
Dr. Anna Olsson-Brown
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • check point inhibitors (CPIs)
  • immunotherapy
  • irAEs
  • immune checkpoint inhibitors (ICIs)
  • survivorship
  • long-term toxicity
  • steroid refractory
  • biologics
  • CAR-T
  • TILs

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Published Papers (4 papers)

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Research

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14 pages, 925 KiB  
Article
Late-Onset Immune-Related Adverse Events in Patients with Advanced Melanoma: The LATENT Study
by Javier Pozas, Sowmya Cheruvu, Poorni Priya Jaganathan, Priya Ganesan, Arjun Modi, James Larkin, Laura Cossar, Anna Olsson-Brown, Alexandra Johnson, Nicholas Garbutt, Rebecca Lee, James Jones, Aislinn Macklin-Doherty, Kate Young and LATENT Study Investigators
Cancers 2025, 17(15), 2461; https://doi.org/10.3390/cancers17152461 - 25 Jul 2025
Viewed by 331
Abstract
Background/Objectives: Immune checkpoint inhibitors have significantly transformed the treatment paradigm of advanced melanoma, leading to substantial improvements in survival outcomes. However, this therapeutic success is accompanied by a spectrum of treatment-related adverse events, some of which are increasingly recognised as enduring and non-reversible. [...] Read more.
Background/Objectives: Immune checkpoint inhibitors have significantly transformed the treatment paradigm of advanced melanoma, leading to substantial improvements in survival outcomes. However, this therapeutic success is accompanied by a spectrum of treatment-related adverse events, some of which are increasingly recognised as enduring and non-reversible. Whilst early-onset immune-related toxicities have been well characterized, late-onset toxicities, often emerging in patients with long-term disease control, remain understudied and are frequently overlooked. Methods: To address this knowledge gap, we conducted a retrospective multicentre study in three UK tertiary referral centres, exploring immune-related adverse events in 246 patients with melanoma who received immune checkpoint inhibitors in the advanced setting. We defined late-onset immune-related adverse events as those occurring at least 3 months after the last cycle of immune checkpoint inhibitors. Results: Although most patients experienced early-onset toxicity, almost 15% of patients developed late-onset immune-related adverse events, including skin rash, colitis, hepatitis, and arthritis, among others. These were often challenging to manage and necessitated the use of systemic steroids. Up to 2% of patients presented ultra-late-onset toxicities, defined as those events occurring at least 12 months after treatment completion. Conclusions: This study provides valuable insights into the characteristics of late-onset immune-related adverse events. To further advance our understanding of these late-onset toxicities, dedicated prospective studies are needed to assess risk factors associated with their development and their impact on quality of life. Additionally, translational research focused on finding predictive biomarkers is essential to identify patients at a higher risk of developing delayed adverse events and to understand how best to manage them. Full article
(This article belongs to the Special Issue Immune-Related Adverse Events in Cancer Immunotherapy)
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13 pages, 503 KiB  
Article
Neutrophil to Lymphocyte Ratio as a Biomarker for the Prediction of Cancer Outcomes and Immune-Related Adverse Events in a CTLA-4-Treated Population
by Michael M. Cunningham, Rachel Romero, Carolina Alvarez, Shruti Saxena Beem, Todd A. Schwartz and Rumey C. Ishizawar
Cancers 2025, 17(12), 2011; https://doi.org/10.3390/cancers17122011 - 17 Jun 2025
Viewed by 500
Abstract
Background/Objectives: Immune-related adverse events (irAEs) triggered by immune checkpoint inhibitor therapy (ICI) have been paradoxically associated with both significant morbidity and improved cancer outcomes. While predictive markers for irAEs have been studied in the PD-1 blockade, less is known for their role in [...] Read more.
Background/Objectives: Immune-related adverse events (irAEs) triggered by immune checkpoint inhibitor therapy (ICI) have been paradoxically associated with both significant morbidity and improved cancer outcomes. While predictive markers for irAEs have been studied in the PD-1 blockade, less is known for their role in CTLA-4 inhibition. This study aims to fill this gap by evaluating NLR and irAE incidence in a CTLA-4-treated population. Methods: This study is a single-center retrospective cohort study investigating 111 patients treated with CTLA-4 inhibition (ipilimumab) to assess associations for baseline low NLR values with cancer outcomes and irAE type and incidence. Patient charts were manually reviewed by a single physician, and unclear clinical events were assessed by a second physician reviewer. Results: In this cohort, the occurrence of more than one irAE presentation was associated with an improved cancer outcome, OR 1.48 (1.02, 2.15). When stratified by organ-specific manifestation, only endocrinologic irAEs were associated with improved cancer outcome, OR 2.82 (1.19, 6.67). A low baseline NLR was statistically significantly associated with an increased incidence of irAEs of any type, OR 4.34 (1.73, 10.9). Conclusions: These data show that irAE occurrence in cancer patients treated with CTLA-4 inhibition is associated with improved cancer outcomes, similar to that previously seen with PD-1 inhibition. It also suggests that the NLR may serve as a practical peripheral biomarker to predict both cancer response and odds of irAEs in patients treated with CTLA-4 inhibition. This low-cost and widely available tool could provide additional information for modeling cancer outcomes. Full article
(This article belongs to the Special Issue Immune-Related Adverse Events in Cancer Immunotherapy)
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Review

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27 pages, 1142 KiB  
Review
Hepatotoxicity in Cancer Immunotherapy: Diagnosis, Management, and Future Perspectives
by Alberto Savino, Alberto Rossi, Stefano Fagiuoli, Pietro Invernizzi, Alessio Gerussi and Mauro Viganò
Cancers 2025, 17(1), 76; https://doi.org/10.3390/cancers17010076 - 29 Dec 2024
Cited by 2 | Viewed by 3015
Abstract
Cancer immunotherapy, particularly immune checkpoint inhibitors, has positively impacted oncological treatments. Despite its effectiveness, immunotherapy is associated with immune-related adverse events (irAEs) that can affect any organ, including the liver. Hepatotoxicity primarily manifests as immune-related hepatitis and, less frequently, cholangitis. Several risk factors, [...] Read more.
Cancer immunotherapy, particularly immune checkpoint inhibitors, has positively impacted oncological treatments. Despite its effectiveness, immunotherapy is associated with immune-related adverse events (irAEs) that can affect any organ, including the liver. Hepatotoxicity primarily manifests as immune-related hepatitis and, less frequently, cholangitis. Several risk factors, such as pre-existing autoimmune and liver diseases, the type of immunotherapy, and combination regimens, play a role in immune-related hepatotoxicity (irH), although reliable predictive markers or models are still lacking. The severity of irH ranges from mild to severe cases, up to, in rare instances, acute liver failure. Management strategies require regular monitoring for early diagnosis and interventions, encompassing strict monitoring for mild cases to the permanent suspension of immunotherapy for severe forms. Corticosteroids are the backbone of treatment in moderate and high-grade damage, alone or in combination with additional immunosuppressive drugs for resistant or refractory cases. Given the relatively low number of events and the lack of dedicated prospective studies, much uncertainty remains about the optimal management of irH, especially in the most severe cases. This review presents the main features of irH, focusing on injury patterns and mechanisms, and provides an overview of the management landscape, from standard care to the latest evidence. Full article
(This article belongs to the Special Issue Immune-Related Adverse Events in Cancer Immunotherapy)
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Other

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15 pages, 1444 KiB  
Systematic Review
Management of Triple M Syndrome: A Narrative Review of Immune Checkpoint Inhibitor-Induced Myasthenia Gravis, Myositis and Myocarditis
by Martin Furlepa, Isabella Watts and Aisling S. Carr
Cancers 2025, 17(13), 2063; https://doi.org/10.3390/cancers17132063 - 20 Jun 2025
Viewed by 1037
Abstract
Background: The advent of immunotherapy has revolutionised cancer treatment by harnessing the immune system to target tumour cells. However, there is increasing awareness of immunotherapy-related adverse events, which can be severe and even fatal. While system-specific immune-related adverse events (ir-AEs) are well documented, [...] Read more.
Background: The advent of immunotherapy has revolutionised cancer treatment by harnessing the immune system to target tumour cells. However, there is increasing awareness of immunotherapy-related adverse events, which can be severe and even fatal. While system-specific immune-related adverse events (ir-AEs) are well documented, growing evidence suggests the existence of overlap syndromes—distinct clusters of immune-mediated complications. One such syndrome is the overlap of myasthenia gravis, myositis and myocarditis, collectively known as Triple M (3M) syndrome. This syndrome is complex, varying in presentation and severity, with in-hospital mortality rates approaching 40%. Whilst there is consensus on the management of system-specific complications, there is no consensus guidance for the management of these overlap syndromes. Methods: In this paper, we conduct a review of the literature, analysing reported cases of 3M syndrome, focusing on treatment approaches and patient outcomes at an individual level. Conclusions: This review highlights the complexity of diagnosing and managing 3M syndrome due to inconsistent reporting, lack of standardised criteria for diagnosis, and treatment variability. While evidence remains limited, we offer broad clinical recommendations and underscore the urgent need for consensus definitions, prospective data collection, and structured treatment guidance. Full article
(This article belongs to the Special Issue Immune-Related Adverse Events in Cancer Immunotherapy)
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