Immunotherapy最新文献

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a debilitating inflammatory disease associated with high recurrence rates and limited response to current therapies. Tezepelumab, a human monoclonal antibody targeting thymic stromal lymphopoietin (TSLP), has emerged as a promising upstream biologic intervention. In the phase 3 WAYPOINT trial, tezepelumab significantly reduced nasal polyp score (-2.07), nasal congestion severity (-1.03), and SNOT-22 scores (-28.4), while decreasing the need for endoscopic sinus surgery by 98% versus placebo. Post hoc analyses of the NAVIGATOR trial showed SNOT-22 improvements (-21.06 vs -10.48 placebo), and PATHWAY data confirmed reductions in asthma exacerbations (up to 85%) and suppression of type 2 inflammatory biomarkers including eosinophils, FeNO, IL-5, and IL-13. Tezepelumab demonstrated a favorable safety profile without increased risk of serious infection or hypersensitivity. Although not approved for CRSwNP, tezepelumab is a promising investigational agent for patients with corticosteroid-refractory or biologic-insensitive disease. Ongoing trials such as ESSENCE will clarify its long-term efficacy, safety, and positioning relative to existing monoclonal antibodies.

Although PD-1 checkpoint inhibition has improved outcomes for some cancer types, a substantial proportion of solid tumors still do not respond, in part due to inadequate cytotoxic CD8+ T-cell infiltration and survival within the tumor microenvironment (TME). CD25+ regulatory T-cells (Tregs) are a subset of T-cells that play a key role in suppressing CD8+ T-cell activity. Depletion of Tregs in the TME could thus enhance anti-cancer immune responses. Here, we present the experience of a patient with platinum-resistant ovarian carcinoma who achieved a durable partial response on a phase 1 clinical trial of an anti-CD25 antibody-drug conjugate combined with pembrolizumab. Notably, her tumor response correlated with a reduction in CD25+ Tregs on paired tumor biopsies and further deepened after treatment discontinuation. This case provides early proof-of-concept that Treg depletion combined with PD-1/PD-L1 inhibitors can lead to anti-cancer efficacy in refractory diseases and offers key lessons to guide future development of anti-Treg therapeutics.

A 58-year-old woman presented to the outpatient clinic with invalidating bone pain in the proximal lower extremities. Laboratory testing showed increased inflammation parameters with a normocytic anemia. Bone scintigraphy revealed increased uptake in both radii, distal femurs, tibiae, and fibulae. PET/CT scanning showed irregular sclerotic bone lesions without other abnormalities. Multiple bone biopsies showed histiocytes expressing CD68 and Factor XIIIa. Metastatic or hematopoietic neoplasms were ruled out. A diagnosis of Erdheim-Chester disease (ECD) with solely osseous involvement was made. Treatment with tocilizumab weekly, an IL-6 receptor antibody, was successful. Tocilizumab appears to be a promising agent for the treatment of patients with Erdheim-Chester disease with limited organ involvement.

Immunotherapy has revolutionized oncology therapeutics landscape. Chimeric Antigen Receptor T-cell (CAR-T) immunotherapy, a form of adoptive cell therapy (ACT) designed to target and kill cancer cells, has shown remarkable success in the treatment of hematological cancer. However, its efficacy against solid tumors remains limited. Phytomedicines represent promising adjuvants to overcome current limitations in cancer immunotherapy due their active compounds that can regulate immune cell functions, modulate immune checkpoint pathways, and reshape the tumoral microenvironment (TME). Current research investigating the TME-modulating effects of certain phytomedicines supports their potential integration as immunotherapy adjuvants. This review focuses on phytomedicines with demonstrated anticancer and immunomodulatory properties, some of which are currently being tested in clinical trials for cancer patients. Despite this promise, significant hurdles persist in the development of phytomedicines as reliable adjuvants in cancer immunotherapy. Consequently, rigorous and focused research is essential to validate their efficacy and safety in this context.

Aims: To evaluate the myeloprotective effects, safety, and survival outcomes of trilaciclib in first-line chemotherapy for extensive-stage small cell lung cancer (ES-SCLC) in China.

Methods: A single-center, retrospective study was conducted with 120 ES-SCLC patients receiving chemotherapy plus immunotherapy between January 2020 and January 2024. Patients were divided into a trilaciclib group (n = 60) and a control group (n = 60). The groups were compared for chemotherapy-related adverse effects, efficacy (ORR, DCR), and survival (PFS, OS).

Results: Trilaciclib significantly reduced the incidence of grade 3-4 neutropenia (18.3% vs. 66.7%, p < 0.001), grade ≥ 3 anemia (13.3% vs. 33.3%, p = 0.010), and thrombocytopenia (10.0% vs. 26.7%, p = 0.018). Median PFS was significantly longer in the trilaciclib group (6.2 vs. 4.7 months, p = 0.0139, HR = 0.6238, 95%CI 0.4474-0.9826), but no significant difference was observed in OS (15.6 vs. 13.8 months, p = 0.2399, HR = 0.8053, 95%CI 0.5577-1.163). The ORR was similar between the two groups (73.3% vs. 63.3%, p = 0.239).

Conclusions: Trilaciclib demonstrates myeloprotective benefits in first-line treatment of ES-SCLC, with significant reductions in chemotherapy-related myelosuppression and improvements in treatment adherence. Although PFS was improved, no significant differences in OS or ORR were observed, indicating the need for further research with larger sample sizes to confirm its clinical efficacy.

The benefits of immune checkpoint inhibitor (ICI)-based treatment are tempered by immune-related adverse events (irAEs). However, various aspects of the pathogenesis of these events remain unclear. Here, we report the case of a 69-year-old patient with advanced hepatocellular carcinoma (HCC) developing severe anemia after 15 cycles of atezolizumab/bevacizumab. The initial workup based on bone marrow aspirate demonstrated selective deficiency of the erythroid line, CD8+ T-cell infiltrate, and Parvovirus B19 PCR (PVB19) positivity, suggesting a pure-red cell aplasia (PRCA) secondary to PVB19 infection. The patient received blood transfusion, intravenous immunoglobulin, and temporary atezolizumab/bevacizumab treatment interruption. After discharge, due to good clinical condition and stable Hb values, atezolizumab/bevacizumab therapy was resumed; however, after three cycles of re-treatment, a recurrence of anemia necessitating blood transfusions every 10 days and hyporeticulocytaemia was observed. The bone marrow aspirate was reassessed, and pure ICI-related red blood cell aplasia was suspected. Prednisone treatment (1 mg/kg per day) was initiated, resulting in progressive improvement of hemoglobin levels without the need for blood transfusion. After resolution of the anemia, treatment with atezolizumab was resumed without recurrence of anemia. This case highlights the potential for atezolizumab to be associated with hematological adverse events, possibly in conjunction with a PVB19 infection.

There is an unmet need for newer treatment options in immune thrombocytopenia (ITP) that address its underlying complex immune dysregulation, induce durable platelet responses, are well tolerated, and improve fatigue and overall quality of life. Rilzabrutinib, an oral, reversible covalent Bruton tyrosine kinase (BTK) inhibitor, is effective through its multi-immune modulation mechanisms by inhibiting B-cell activation, possibly decreasing autoantibody production, preventing FcγR-mediated phagocytosis in the spleen and liver, and reducing chronic inflammation.Preclinical studies of rilzabrutinib in immune-mediated disease settings demonstrated high selectivity, full reversibility, and durable BTK occupancy. Oral rilzabrutinib 400 mg BID demonstrated rapid, durable platelet count increases in patients with persistent/chronic ITP in the phase 2 LUNA2 study and significantly improved durable platelet response vs placebo in the pivotal phase 3 LUNA3 trial. Additionally, rilzabrutinib improved multiple disease aspects including fatigue and bleeding with a well-tolerated safety profile.Through multi-immune modulation, rilzabrutinib achieves rapid and durable platelet response, improves fatigue, and decreases bleeding in ITP patients. It is well tolerated with an acceptable safety profile. Efficacy may be increased if administered earlier in the course of disease. Longer-term studies, and investigations in pediatric patients and other immune-mediated diseases are underway.

Non-small cell lung cancer (NSCLC) accounts for over 80% of lung cancer cases and is often diagnosed at advanced stages. Resistance to immunotherapy in NSCLC involves genetic mutations, tumor microenvironment (TME) characteristics, treatment history, and age-related factors. Despite increasing use of immune checkpoint inhibitors (ICIs), resistance mechanisms remain poorly understood. Key genetic alterations associated with resistance include STK11, KEAP1, and EGFR mutations, particularly with low tumor mutational burden (TMB). The immunosuppressive tumor microenvironment, characterized by regulatory T cells and myeloid-derived suppressor cells, can hinder ICI efficacy. Metabolic alterations and deficient antigen presentation contribute to resistance. Prior treatments can alter the tumor microenvironment, affecting subsequent immunotherapy responses. Age-related factors, including immunosenescence, influence resistance, with older patients having higher TMB and more immunogenic microenvironments. Strategies to overcome resistance include combination therapies, biomarker-driven approaches, and targeting novel pathways. Combining ICIs with chemotherapy or radiation can enhance antitumor responses. Biomarker approaches, such as TMB and PD-L1 expression assessment, help tailor therapies. Exploring novel targets like RIG-I and STING pathways may provide additional solutions. Understanding these factors is crucial for developing personalized strategies to overcome immunotherapy resistance in NSCLC.

Aim: A translational multiscale approach, encompassing tumor immune microenvironment (TIME), circulating immune-inflammatory benchmarks, and transcriptomic profiles, was undertaken to identify prognostic biomarkers of immunotherapy (IT) efficacy in patients with advanced pleural mesothelioma (PM).

Methods: Advanced PM patients (n = 17) treated with nivolumab plus ipilimumab were prospectively enrolled in the FIL-QI 2021 study. Baseline blood and tumor samples were analyzed for immune subsets and functional markers (Granzyme B, Ki67) by flow cytometry, cytokines by multiplex ELISA, TILs and PD-L1 by immunohistochemistry, and gene expression by nanostring. Associations with overall survival (OS), progression-free survival (PFS), time-to-treatment failure (TTF), and modified disease control rate (mDCR) were assessed.

Results: Higher baseline CD4⁺ GnzB⁺ T cells were significantly associated with OS ≥ 12 months (p < 0.001), PFS ≥ 6 months (p = 0.027), and TTF ≥ 6 months (p = 0.016), along with lower CD14⁺ monocytes (PFS: p = 0.038). Elevated proliferating CD8⁺ Ki67⁺ T cells (PFS: p = 0.038; TTF: p = 0.022) also predicted improved outcomes. Low IL-2 levels correlated with OS ≥ 12 months (p = 0.02). TIME analysis showed higher intratumor CD4⁺ TILs (p = 0.03) and CD4/CD8 ratio (p = 0.016) in long survivors. Transcriptomics revealed nine genes differentially regulated according to clinical outcomes, among which ULBP2 emerged as a strong predictor of poor prognosis (LASSO-Cox regression model).

Conclusion: Parallel immune and transcriptomic profiling identifies biomarkers predictive of IT benefit in PM.