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Cancers
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Cancer Immunotherapy-Related Adverse Events and Therapy-Related Accelerated Aging
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Cancer Immunotherapy-Related Adverse Events and Therapy-Related Accelerated Aging

A Special Issue of Cancers (ISSN 2072-6694) belonging to the section "Cancer Immunology and Immunotherapy".

Deadline for manuscript submissions: 30 September 2026 | Viewed by 1548

Editor

Prof. Dr. Grace Lu-Yao

E-Mail Website
Guest Editor
Sidney Kimmel Cancer Center at Jefferson, Philadelphia, PA, USA
Interests: cancer surveillance, screening, and treatment for prostate cancer; outcomes research and cancer epidemiology; host factors and immunotherapy outcomes
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

As immunotherapy continues to revolutionize cancer treatment, understanding the risks and consequences associated with immune-related adverse events (irAEs) has become increasingly urgent. This Special Issue invites original research, reviews, and commentaries focused on the intersection of patient and tumor characteristics, patterns of irAE development, and emerging long-term complications—including accelerated aging—among individuals treated with immunotherapeutic agents.

We are particularly interested in studies that address the following:

  • Host and tumor determinants of irAE risk, including immune profiles, genetic predisposition, comorbidities, and tumor microenvironmental factors;
  • Timing and patterns of irAEs, including early vs. delayed onset, chronic toxicities, and their implications for treatment outcomes;
  • Organ-specific and multisystemic complications, including severity grading, reversibility, and impact on survival or treatment discontinuation;
  • Mechanisms and manifestations of accelerated aging in immunotherapy recipients, such as frailty, neurocognitive changes, or cardiovascular decline;
  • Predictive biomarkers and clinical algorithms for risk stratification and the early detection of irAEs;
  • Intervention strategies, both prophylactic and therapeutic, aimed at mitigating irAEs while preserving anti-tumor efficacy;
  • Real-world data and survivorship outcomes that inform long-term monitoring and management frameworks.

Through this issue, we aim to deepen the collective understanding of irAE biology and improve patient-centered immunotherapy delivery. Submissions from multidisciplinary teams—including oncology, immunology, geriatrics, and survivorship research—are highly encouraged.

Prof. Dr. Grace Lu-Yao
Guest Editor

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 250 words) can be sent to the Editorial Office for assessment.

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-anonymized 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

  • immune-related adverse events (irAEs)
  • accelerated aging
  • immunotherapy

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Published Papers (2 papers)

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Research

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13 pages, 1231 KB  
Article
Incidence and Clinical Impact of Endocrinopathy Following First-Line Nivolumab-Plus-Relatlimab Therapy for Metastatic Melanoma
by Julia Reitkopp, Wolfram Samlowski and Mahir Hasan
Cancers 2026, 18(14), 2349; https://doi.org/10.3390/cancers18142349 - 21 Jul 2026
Viewed by 467
Abstract
Background: Dual immune checkpoint inhibitor therapy with nivolumab plus relatlimab has substantial clinical activity against metastatic melanoma. The incidence and timing of endocrine immune-related adverse events with this treatment remain poorly characterized. Methods: We conducted a retrospective record review of 52 sequential patients [...] Read more.
Background: Dual immune checkpoint inhibitor therapy with nivolumab plus relatlimab has substantial clinical activity against metastatic melanoma. The incidence and timing of endocrine immune-related adverse events with this treatment remain poorly characterized. Methods: We conducted a retrospective record review of 52 sequential patients who received nivolumab plus relatlimab as initial therapy for metastatic cutaneous melanoma. All patients underwent sequential endocrine screening (TSH, FT4, ACTH, cortisol) prior to each monthly treatment cycle. The incidence and onset of hypothyroidism and hypopituitarism were evaluated, as was cancer treatment outcome. Results: Biochemical evidence for endocrinopathy was identified in 25% of patients. This included a 13.5% incidence of hypothyroidism (median onset 79.0 ± 63.9 days) and 11.5% incidence of hypopituitarism (median onset 243.5 ± 75.6 days). Due to screening and early replacement therapy, there were no related hospitalizations. Patients who developed endocrinopathy showed a trend toward improved progression-free and overall survival. An exploratory analysis suggested that the incidence of endocrinopathy was significantly lower in patients treated with nivolumab plus relatlimab than in those treated with ipilimumab plus nivolumab. Conclusions: During treatment with nivolumab plus relatlimab, endocrinopathy developed in approximately 25% of metastatic melanoma patients, emphasizing a need for screening testing. In an exploratory analysis, endocrinopathy appeared less frequent than in ipilimumab-plus-nivolumab-treated patients. Recovery from endocrinopathy appeared uncommon. Development of delayed endocrinopathy following elective treatment discontinuation for patients in remission was rare (3.8%). Patients who developed endocrinopathy showed a trend toward improved clinical outcome. Full article
(This article belongs to the Special Issue Cancer Immunotherapy-Related Adverse Events and Therapy-Related Accelerated Aging)
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Review

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20 pages, 3474 KB  
Review
Checkpoint Blockade and Acquired Humoral Immune Dysregulation: Emerging Evidence for Antibody Deficiency During Long-Term PD-1/PD-L1 Inhibition
by Velizar Shivarov
Cancers 2026, 18(15), 2472; https://doi.org/10.3390/cancers18152472 - 1 Aug 2026
Viewed by 578
Abstract
Immune checkpoint inhibitors have transformed the treatment of multiple malignancies by restoring antitumor T-cell activity. Their clinical identity is therefore that of immune-enhancing therapies. However, the biology of the PD-1/PD-L1 axis is more complex than simple immune inhibition. Human inborn errors of PD-1 [...] Read more.
Immune checkpoint inhibitors have transformed the treatment of multiple malignancies by restoring antitumor T-cell activity. Their clinical identity is therefore that of immune-enhancing therapies. However, the biology of the PD-1/PD-L1 axis is more complex than simple immune inhibition. Human inborn errors of PD-1 or PD-L1 signaling indicate that this pathway contributes to immune homeostasis, tolerance, protection against selected infections, and the development of memory B cells and antibody responses. These observations raise an important translational question: Can prolonged pharmacologic blockade of PD-1 or PD-L1 can, in selected clinical contexts, induce or reveal acquired humoral immune dysfunction? This review synthesizes evidence linking PD-1/PD-L1 disruption to altered class-switched memory B-cell biology, antibody responses, vaccine immunogenicity, infection susceptibility, and secondary antibody deficiency. It also incorporates emerging evidence that checkpoint blockade may expand age-associated B cells, a population associated with impaired neutralizing antibody responses after vaccination, and counterbalances evidence that vaccination during ICI therapy may enhance antitumor immunity and survival. Current clinical evidence does not establish the incidence, prevalence, reversibility, dose dependence, or causality of an ICI-induced antibody-deficiency syndrome. Instead, the available data support a hypothesis-generating model of heterogeneous humoral remodeling, ranging from preserved or enhanced vaccine-associated immune activation to qualitative antibody failure and secondary antibody deficiency in susceptible patients. Future studies should incorporate baseline and longitudinal measurements of immunoglobulins, vaccine-specific and neutralizing antibodies, class-switched memory B cells, age-associated B cells, plasmablasts, infection burden, and exposure to immunosuppressive treatment. Full article
(This article belongs to the Special Issue Cancer Immunotherapy-Related Adverse Events and Therapy-Related Accelerated Aging)
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