Immune check point inhibitors for ocular adnexal and periocular tumors

Taiwan Journal of Ophthalmology, Journal Year: 2025, Volume and Issue: 15(1), P. 14 - 25

Published: Jan. 1, 2025

Abstract: The introduction of immune checkpoint inhibitors (ICIs) into clinical medicine has resulted in more robust response rates for various malignancies, including metastatic and locally advanced periocular ocular tumors. Their increased utility constitutes a pivotal shift from invasive surgical treatments allowing patients to proceed with eye preserving therapies while also achieving local tumor control. aim this review article is provide summary updates on the current ICIs conjunctival melanoma squamous cell carcinoma, Merkel carcinoma basal resistant BRAF inhibitors. A literature search was conducted PubMed programmed death protein 1 (nivolumab, pembrolizumab), PD-L1 (atezolizumab, avelumab, durvalumab), CTLA-4 (ipilimumab, tremelimumab) along previously noted While references several large trials cutaneous tumors, most data are limited case reports series. Our overall presents promising results usage ICI patients, noting an survival rate, control disease decreased morbidity, avoiding orbital exenteration. These improvements have not come without considerations adverse immune-related side effects clinicians needs be judicious deciding between efficacy effects.

Language: Английский

---

Hepatic immune-related adverse event increased the overall survival of patients with malignancies treated with immune checkpoint inhibitors

Hepatology International, Journal Year: 2025, Volume and Issue: unknown

Published: April 8, 2025

Language: Английский

---

Emerging roles of checkpoint molecules on B cells

Immunological Medicine, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 12

Published: Jan. 17, 2025

Immune checkpoint molecules, including both co-inhibitory molecules and co-stimulatory are known to play critical roles in regulating T-cell responses. During the last decades, immunotherapies targeting these (such as programmed cell death 1 (PD-1), lymphocyte activation gene 3 (LAG-3)) have provided clinical benefits many cancers. It is becoming apparent that not only T cells, but also B cells a capacity express some molecules. These were originally thought be markers for regulatory which produce IL-10, recent studies suggest (especially immunoglobulin mucin domain (TIM-1), immunoreceptor with Ig ITIM domains (TIGIT), PD-1) can regulate intrinsic B-cell functions. Here, we focus on summarize their characteristics, ligands, functions cells.

Language: Английский

---

Early-Stage Renal Cell Carcinoma: Who Needs Adjuvant Therapy?

Biomedicines, Journal Year: 2025, Volume and Issue: 13(3), P. 543 - 543

Published: Feb. 21, 2025

Surgery is the oldest modality of kidney cancer therapy and usually first step in treatment process. To improve surgical outcomes, adjuvant frequently administered to eliminate residual tumors reduce risk recurrence metastasis. However, not all patients require treatment. The decision regarding whether treat or renal cell carcinoma depends on recurrence, including tumor stage histology, clinical, biological, personal factors. This article will address challenges treating with review current evidence ongoing clinical trials.

Language: Английский

---

Antibody-Free Immunopeptide Nano-Conjugates for Brain-Targeted Drug Delivery in Glioblastoma Multiforme

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 12, 2025

Glioblastoma Multiforme (GBM) represents a significant clinical challenge amongst central nervous system (CNS) tumors, with dismal mean survival rate of less than 8 months, statistic that has remained largely unchanged for decades (National Brain Society, 2022). The specialized intricate anatomical features the brain, notably blood-brain barrier (BBB), pose challenges to effective therapeutic interventions, limiting potential reach modern advancements in immunotherapy impact these types tumors. This study introduces an innovative, actively targeted immunotherapeutic nanoconjugate (P12/AP-2/NCs) designed serve as agent capable traversing BBB via LRP-1 receptor-mediated transcytosis. P12/AP-2/NCs exert its immune-modulating effects by inhibiting PD-1/PD-L1 axis through small-size PD-L1/ PD-L2 antagonist peptide Aurigene NP-12 (P12). are synthesized from completely biodegradable, functionalized high molecular weight β-poly(L-malic acid) (PMLA) polymer, conjugated P12 and Angiopep-2 (AP2) yield P12/AP-2/NCs. Evaluating nanoconjugates permeability 3-D tumor model efficacy using vitro BBB-Transwell spheroid based demonstrating successful crossing internalization brain 3D environments. In addition, mediated T cell's cytotoxicity on region death U87 GBM model. AP2/P12/NCs is selectively inhibited PD1/PDL1 interaction cells site, increasing inflammatory cytokine secretion cell proliferation. in-vivo murine environment, rhodamine fluorophore-labeled displayed significantly increased accumulation during 2-6 h time intervals post-injection prolonged bioavailability over unconjugated peptides. demonstrated safety profile at both low doses major organ histopathology evaluations. Our findings introduce novel, programmable platform penetrating directed delivery small peptides immune environment modulation without utilizing antibodies, offering promise treating challenging diseases like glioblastoma multiforme beyond.

Language: Английский

---

Type I Diabetes—A Rare Adverse Event Described in Patients Receiving Immunotherapy Versus a Side Effect from SARS-CoV-2 Infection

Reports — Medical Cases Images and Videos, Journal Year: 2025, Volume and Issue: 8(1), P. 31 - 31

Published: March 14, 2025

Introduction and Clinical Significance: Lung cancer, a leading cause of global cancer diagnoses, maintains the highest mortality risk despite advances in treatment. Immunotherapy agents, such as anti-programmed death-1/programmed death ligand-1 (PD-1/PD-L1), have revolutionized care for non-small cell lung (NSCLC). However, success is tempered by emergence immune-mediated adverse reactions, including rare onset type I diabetes. The incidence diabetes mellitus increased during SARS-CoV-2 pandemic. While there are several cases new-onset after COVID-19 vaccination, no case 1 was described an immune checkpoint inhibitor (ICI)-treated patient. Case Presentation: A 57-year-old male with stage IV NSCLC (brain liver metastases) who had been treated nivolumab 4 years appeared positive infection at routine check. After two weeks, he admitted to our clinic severe fatigue, hyperglycemia, hyponatremia, hyperkalemia. HbA1c level normal serum peptide C undetectable. Nivolumab treatment ceased, patient became fully dependent on basal–bolus insulin. 3 months, showed complete imagistic remission. Conclusions: presented significant challenges due unclear etiology newly uncommon age which developed. outcome suggests that anti-PD-1 can act synergistically.

Language: Английский

---

Correlative analysis of immune-related thyroid dysfunction and prognosis in patients with advanced esophageal squamous cell carcinoma

Anti-Cancer Drugs, Journal Year: 2025, Volume and Issue: unknown

Published: March 20, 2025

To explore the clinical characteristics of immune-related thyroid dysfunction (TD) and its correlation with prognosis. By collecting data 116 patients advanced esophageal squamous cell carcinoma (ESCC) who received programmed death receptor-1 (PD-1) inhibitor treatment, we analyzed TD influencing factors compared prognostic differences among in different groups. Immune-related occurred 45 (38.8%) after PD-1 median time to occurrence was 11.3 weeks. The toxicity grade 1 or 2 only required symptomatic treatment. Female patients, as well those an Eastern Cooperative Oncology Group Performance Status less than equal 1, no lymph node metastasis, history drinking, high baseline thyroid-stimulating hormone levels, were likely develop TD. Compared group without [TD(−)], progression-free survival (mPFS) overall (mOS) [TD(+)] significantly prolonged (mPFS: 12.6 vs. 6.5 months, P = 0.001; mOS: 20.2 11.2 < 0.001). Further subgroup analysis showed that overt (Overt_TD), Overt_TD had a longer PFS 12.4 7.3 0.015) OS (mOS: 12.2 60-, 90-, 120-day landmark further confirmed associated improvement OS. Multivariate Cox regression indicated independent factor for ( 0.004). is very common adverse event. It safe manageable has potential value ESCC treated inhibitors.

Language: Английский

---

Incidence and impact of immune combination therapies adverse events in advanced renal cell carcinoma patients

Immunotherapy, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 10

Published: March 28, 2025

Immune (IO)-combination therapies have revolutionized the treatment of advanced renal cell carcinoma (aRCC) but are more frequently associated with adverse events (AEs) compared to tyrosine kinase inhibitors (TKI) alone. This retrospective study aimed evaluate incidence and prognostic significance AEs in patients receiving combination therapies. We included treated nivolumab/ipilimumab (NI), nivolumab/cabozantinib (NC), or pembrolizumab/axitinib (PA) at four Italian oncology centers between November 2023 June 2024. The impact on progression-free survival (PFS), overall (OS), response, disease control rate were analyzed using descriptive statistics, Kaplan-Meier method, Cox regression. occurred 78.8% NI, 87.9% NC, 92.3% PA patients. Grade 3-4 common IO-TKI vs. IO-IO combinations (32.9% 15.1%, p = 0.05). Pruritus pulmonary frequent IO-IO, while hypertension mucositis IO-TKI. High-grade did not PFS OS, TKI reduction due was longer OS (p < 0.01). Steroid use also improved 0.04). ICI-based for RCC. While they do negatively affect survival, their management, especially through dose reductions steroids, may improve outcomes.

Language: Английский

---

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, Journal Year: 2025, Volume and Issue: unknown

Published: April 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.

Language: Английский

---

Adverse events after nivolumab and ipilimumab combined immunotherapy in advanced renal cell carcinoma: a multicentre experience in Poland

BMC Cancer, Journal Year: 2024, Volume and Issue: 24(1)

Published: Nov. 15, 2024

Abstract Background Immune checkpoint inhibitors (ICIs) have been employed in the adjuvant and metastatic setting of renal cell carcinoma (RCC) treatment. Among ICIs, combined immunotherapy has highest risk for immune-related adverse events (irAEs). We aimed to document incidence irAEs RCC patients treated with nivolumab ipilimumab as data from European population remain limited. Materials methods analysed 88 + between May 2022 June 2024 across six high-volume oncology units Poland. reviewed estimated their impact on survival parameters via univariate multivariate Cox proportional hazards regression models, along log-rank tests. Results With a median follow-up 11.3 months, overall (OS) was not reached, whereas progression-free (PFS) 12.8 months (6.3–19.3). A total 74 were recorded 50 patients. The most frequent endocrine ( n = 20, 27%), hepatic 15, 17%), general 12, 13.6%), cutaneous 11, 12.5%). occurrence associated 60% lower disease progression (hazard ratio 0.44, 95% confidence interval 0.2–0.87, p 0.018) without impacting OS higher control rate 45, 90% vs. 24, 63.2%, 0.004). In contrast, hepatotoxicity had poorer outcomes, 2.6-fold greater death 0.05). Conclusions IrAEs may serve predictive factor efficacy regimen Special attention is needed hepatotoxicity, it can significantly outcomes.

Language: Английский

---