Peripheral blood cell counts as predictors of immune-related adverse events in cancer patients receiving immune checkpoint inhibitors: a systematic review and meta-analysis

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Янв. 30, 2025

Background In recent years, immune checkpoint inhibitors (ICIs) have shown significant efficacy in treating various malignancies and become a key therapeutic approach cancer treatment. However, while ICIs activate the system, they can also induce immune-related adverse events (irAEs). Due to variability frequency severity of irAEs, clinical management faces challenge balancing antitumor with risk irAEs. Predicting preventing irAEs during early stages treatment has critical research focus immunotherapy. This study aims evaluate predictive value peripheral blood cell counts for Methods Studies meeting inclusion criteria were identified through database searches. The standardized mean difference (SMD) was used compare continuous counts. For studies that did not provide adjusted odds ratios (ORs) 95% confidence intervals (CIs), crude ORs categorized calculated. protocol registered on PROSPERO (CRD42024592126). Results meta-analysis included 60 involving 16,736 patients treated ICIs. Compared without those experiencing had significantly higher baseline ALC (SMD = 0.12, CI 0.01-0.24), ANC -0.18, -0.28 -0.07) PLR -0.32, -0.60 -0.04) lower. Similarly, indicated (OR 2.46, 1.69-3.57) AEC 2.05, 1.09-3.85), along lower NLR 0.64, 0.50-0.81) 0.63, 0.48-0.82), associated an increased Subgroup analysis further cutoff values (2×10^9/L), (5 or 3), (180) as better predictors Conclusion Higher AEC, ANC, NLR, PLR, are is needed determine optimal explore predicting specific types Systematic review registration https://www.crd.york.ac.uk/PROSPERO/ , identifier CRD42024592126.

Язык: Английский

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CTLA4 Alteration and Neurologic Manifestations: A New Family with Large Phenotypic Variability and Literature Review

Genes, Год журнала: 2025, Номер 16(3), С. 306 - 306

Опубликована: Март 3, 2025

Cytotoxic-T-lymphocyte-antigen-4 (CTLA-4), a member of the immunoglobulin superfamily, is an essential negative regulator immune responses that constitutively expressed on both regulatory (Treg) and activated T cells. To date, heterozygous germline variants in CTLA4, leading to haploinsufficiency, have been associated with several immunological disorders, including hypogammaglobulinemia, multi-organ autoimmunity, lymphoproliferative enlarged lymphoid organs. Indeed, CTLA4 carriers display highly heterogeneous clinical manifestations phenotypic spectrum ranging from asymptomatic carrier status fatal autoimmunity. Here, we describe family autoimmune phenotypes (Hashimoto thyroiditis, psoriasiform dermatitis, celiac disease/inflammatory bowel disease, rheumatoid arthritis), segregating across three different generations due recurrent missense variant [c.436G>A, p.(Gly146Arg)] gene. Interestingly, proband showed prominent neurological manifestations, seizures, hydrocephalus, demyelination, which are less frequently reported individuals pathogenic CTLA4. A detailed literature review neurologic features so far also provided.

Язык: Английский

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Receiving immunotherapy for the treatment of advanced renal cell carcinoma is associated with higher burden of illness, coagulopathy, cardiac arrhythmia, and disparities

Supportive Care in Cancer, Год журнала: 2025, Номер 33(4)

Опубликована: Март 15, 2025

Язык: Английский

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Gut microbiota in melanoma: effects and pathogeneses

Microbiological Research, Год журнала: 2025, Номер unknown, С. 128144 - 128144

Опубликована: Март 1, 2025

Язык: Английский

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Immune Modulation and Immunotherapy in Solid Tumors: Mechanisms of Resistance and Potential Therapeutic Strategies

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(7), С. 2923 - 2923

Опубликована: Март 24, 2025

Understanding the modulation of specific immune cells within tumor microenvironment (TME) offers new hope in cancer treatments, especially immunotherapies. In recent years, and resistance to immunotherapy have become critical challenges treatments. However, novel strategies for emerged as promising approaches oncology due vital roles immunomodulators regulating progression metastasis modulating immunological responses standard care With progress immuno-oncology, a growing number mechanisms are being uncovered, offering potential enhanced clinical near future. Thus, gaining comprehensive understanding broader context is essential. Herein, we particularly summarize paradoxical role tumor-related cells, focusing on how targeted their actions modulated by immunotherapies overcome immunotherapeutic cells. We also highlight molecular employed tumors evade long-term effects agents, rendering them ineffective.

Язык: Английский

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Combination therapy with immune checkpoint inhibitors in colorectal cancer: Challenges, resistance mechanisms, and the role of microbiota

Biomedicine & Pharmacotherapy, Год журнала: 2025, Номер 186, С. 118014 - 118014

Опубликована: Март 31, 2025

Язык: Английский

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Late-onset recurrent immune checkpoint inhibitor-related pneumonitis after cessation of pembrolizumab: a case report

Immunotherapy, Год журнала: 2025, Номер unknown, С. 1 - 4

Опубликована: Апрель 2, 2025

Immune-related adverse events typically occur during the early phases of immune checkpoint inhibitor therapy. However, late-onset immune-related can still arise long after therapy has ended. Immune inhibitor-related pneumonitis warrants special attention for risk assessment and detection due to its potential serious outcomes, including hospitalization death. Despite rarity, should be considered in differential diagnosis dyspnea patients with a history prevent morbidity mortality. In this case report, we present an 84-year-old female patient suffering from locally advanced triple-negative breast cancer requiring 104 days last cycle pembrolizumab. Following successful treatment corticosteroids, recurrence occurred month later. Corticosteroid was reinitiated, gradually tapered radiological improvement, eventually discontinued. The remains remission cancer. For therapy, medical vigilance, accurate diagnosis, timely management are crucial.

Язык: Английский

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Impact of tumor localization on antitumor immunity with conditionally activated CTLA-4 blockade

Journal for ImmunoTherapy of Cancer, Год журнала: 2025, Номер 13(4), С. e010566 - e010566

Опубликована: Апрель 1, 2025

Background Immune checkpoint blockade (ICB) can induce antitumor efficacy but also induces immune-related adverse events. Systemically administered ICB activate immune cells throughout the host. Conditionally active with proteolytically cleaved masking domains potentially reduce events seen anti-cytotoxic T-lymphocyte associated protein 4 (CTLA-4) antibody. Methods We examined how different formats of a conditionally activated dual variable domain IgG (DVD) that binds CTLA-4 and tumor-associated antigen prostate stem cell (PSCA) lead to in syngeneic subcutaneous metastatic murine tumor models. defined capacity these DVDs modulate responses by multiparameter flow cytometry. Results uncouple from toxicity. A fully cleavable construct (symmetric DVD, sDVD), which be released target cells, showed superior compared asymmetric retains its binding. The sDVD elicited highest tumor-antigen-specific T-cell detected tumors tumor-draining lymph nodes, as well presenting rate intratumoral splenic “non-exhausted” antigen-specific CD8 T cells. SDVD induced degrees memory self-renewal potential. These effects were dependent on PSCA expression tumors. Conclusions findings support notion modulation immunity away is critically important for optimal immunity. bispecific antibody design may enable improved systemic than traditional both primary metastases.

Язык: Английский

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Dermatologic toxicities related to cancer immunotherapy

Toxicology Reports, Год журнала: 2025, Номер unknown, С. 102021 - 102021

Опубликована: Апрель 1, 2025

Язык: Английский

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Plasma cytokine levels in a patient with multiple immune-mediated adverse events on the background of nivolumab therapy for metastatic skin melanoma

Cytokines and inflammation, Год журнала: 2025, Номер unknown

Опубликована: Апрель 16, 2025

Nivolumab, like other immune checkpoint inhibitors, is effective in treating malignant neoplasms. However, immune-mediated adverse events linked to cytokine imbalance are increasingly reported. These include myocarditis, pericarditis, pulmonitis, myositis, and lesions of the joints, intestines, thyroid, often presenting spontaneously with reactive courses. Such phenomena hypothesized stem from system disinhibition autoimmune inflammation involving patient's healthy tissues due cross-sensitivity context imbalance. Case description. A 65-year-old woman was observed for 4 years, starting 2019, when she presented bleeding pigmented growths on her right shin. This later diagnosed as nodular melanoma ulceration mitotic activity. The patient under observation two but 2021, after disease progression, underwent seven cycles nivolumab therapy. Soon after, condition deteriorated, by 2022, had developed acute hematological syndrome, skin hardening, polyneuropathy. She admitted rheumatology department. Blood plasma analysis revealed elevated levels interleukin-1β, MIG, PDGF-AB/BB, RANTES, TGFα. markers indicated an intermediate inflammatory response—less controlled than patients without not severe seen rheumatoid arthritis. Clinical outcome. findings suggested a hybrid process systemic cancer-related component Th17 overactivation, predominance pro-inflammatory mediators typical diseases. Nivolumab discontinued, comprehensive treatment plan implemented manage cardiac, neurological, rheumatic complications. achieved remission melanoma.

Язык: Английский

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