Immunotherapy最新文献

Aim: To determine the impact of antibiotic spectrum of activity and exposure timing on survival outcomes and development of gastritis/colitis.

Methods: We conducted a single-center, retrospective cohort study of 214 patients with advanced, metastatic, or unresectable melanoma treated with immune checkpoint inhibitors. Antibiotic exposure was classified by spectrum of activity (with and without anaerobic coverage) and antibiotic timing. Primary outcomes were the effect of antibiotic administration 30-days prior to starting ICI therapy and during ICI therapy on overall survival (OS) and progression-free survival (PFS).

Results: Antibiotic exposure during ICI was associated with improved OS (HR: 0.57, 95% CI (0.35-0.92), p = 0.023). Use of antibiotics without anaerobic coverage was associated with improved PFS (HR: 0.53, 95% CI (0.32-0.87), p = 0.013), and OS (HR: 0.47, 95% CI (0.24-0.92), p = 0.026). There was a trend toward increased risk of gastritis/colitis with antibiotics without anaerobic coverage during ICI therapy, although this did not reach statistical significance (OR 2.08, 95% CI (0.43-5.46), p = 0.069).

Conclusion: Antibiotic timing and spectrum of activity may be predictive of survival outcomes and risk of developing gastritis/colitis in ICI-treated patients with advanced-stage melanoma. Unlike previous studies, we found improved survival in patients receiving antibiotics during treatment and in those receiving antibiotics without anaerobic coverage.

Over the past decade, immune checkpoint inhibitors (ICIs) have revolutionized oncology care, resulting in sustained clinical remissions and prolonged overall survival. With this remarkable success comes the challenge of managing adverse events. We present a case of a patient with chronic lymphocytic leukemia (CLL) and cutaneous squamous cell carcinoma (cSCC) who received treatment for the advanced cSCC with Cemiplimab. This intervention led to a rapid progression of her hitherto quiescent CLL, and she began treatment for it. Understanding the complex mechanism of action of ICIs and the pathophysiology of lymphoid malignancies is important for the safe use of ICIs.

Small-bowel adenocarcinoma (SBA) is rare and often diagnosed at an advanced stage. We report the case of a 61-year-old man with locally advanced unresectable upper jejunal SBA secondary to metastatic lymph nodes involving the superior mesenteric artery. Initial chemotherapy with FOLFOX (oxaliplatin, fluorouracil, and folinic acid) was initiated; however, a microsatellite instability-high (MSI-H) status was identified, and the treatment was promptly switched to pembrolizumab. After four cycles, marked regression of the metastatic lymph nodes was observed, and conversion surgery was performed. Partial jejunectomy with lymphadenectomy was performed to achieve an R0 resection. Pathological examination revealed a moderately differentiated adenocarcinoma with extensive fibrosis in the metastatic lymph nodes, indicating a substantial response to immunotherapy. The patient remained disease-free for 9 months postoperatively. Additionally, a brief meta-analysis of 10 studies comprising 72 patients with MSI-H/mismatch repair-deficient SBA revealed an objective response rate to immune checkpoint inhibitors of 65.3%. This case highlights the potential of pembrolizumab for the curative resection of an initially unresectable MSI-H SBA.

Metaplastic breast cancer (MpBC) is a rare and aggressive subtype of breast cancer with a poor prognosis. Recent studies have shown that anti-PD-1 therapy is effective in treating this type of cancer. We described a rare case of MpBC during lactation that worsened quickly post-surgery. Despite receiving chemotherapy and immunotherapy, the patient passed away from respiratory failure caused by tumor compression. Subsequent genetic testing revealed the presence of the resistance gene CDKN2A. Lactating women should promptly get checked for abnormal breast symptoms to catch breast cancer early. More research is needed to determine how effective anti-PD-1 therapy is for MpBC. PD-L1 is not usually tested in clinical settings, but it's important to check for CDKN2A when looking at resistance targets for PD-L1.

Background: Immune checkpoint inhibitors (ICIs) are essential for advanced breast cancer, particularly triple-negative breast cancer (TNBC) patients. While effective, they may cause immune-related adverse events (irAEs), including rare cases of cystitis with unclear mechanisms. This study reports a cystitis case following ICI therapy in a recurrent breast cancer patient, exploring potential associations.

Case presentation: A 51-year-old female with recurrent breast cancer (TNBC-like, IM subtype) following a 10-year disease-free interval underwent treatment with a paclitaxel-based chemotherapy regimen combined with camrelizumab. Three weeks after initiating ICI therapy, urinary frequency, urgency, dysuria, and hematuria developed. Urinalysis showed leukocyte esterase 3+, protein 2+, and occult blood 2+, with negative bacterial and fungal cultures. Bladder wall thickening and mild bilateral hydronephrosis were detected on ultrasound. Symptomatic management, including urinary alkalization and anti-inflammatory therapy, resulted in gradual symptom improvement. After discontinuation of camrelizumab, the patient experienced two episodes of cystitis, both of which resolved following treatment with methylprednisolone, with no further episodes observed during subsequent follow-up.

Conclusion: This case highlights a rare presentation of immune-related cystitis associated with ICI therapy in recurrent breast cancer. ICIs may increase cystitis risk through immune-mediated mechanisms, although the underlying pathophysiology remains unclear, warranting further investigation.

Checkpoint blockade has revolutionized cancer therapy, yet durable responses are limited by myeloid-driven immunosuppression. Bexmarilimab, a first-in-class monoclonal antibody targeting the scavenger receptor Clever-1 (Stabilin-1), represents a novel strategy to recondition tumor-associated macrophages and malignant myeloid cells. This review summarizes the biological rationale for Clever-1 targeting, appraises clinical and translational evidence, and outlines strategies to enhance therapeutic efficacy through patient selection, rational drug combinations, biomarker-driven patient stratification, and timing of intervention. We also highlight future opportunities for integrating bexmarilimab with next-generation immunotherapies and precision medicine approaches.

Background: Immune checkpoint inhibitors-induced thrombocytopenia (ICIs-TCP) is a rare immune-related adverse events (irAEs). The physiological changes underlying ICIs-TCP remain incompletely elucidated.

Methods: We performed multi-omics analysis (gut microbiome, plasma metabolomics/proteomics) comparing microbial/metabolic alterations in cancer patients with (n = 8) and without ICIs-TCP (n = 8). Fecal metagenomic shotgun sequencing was performed to assess microbial composition and function, while plasma metabolomics and proteomics analyses identified systemic metabolic and protein expression changes associated with ICIs-TCP.

Results: Patients with ICIs-TCP exhibited distinct gut microbiota profiles, with an increased abundance of Segatella, Prevotella, and Clostridium, alongside a depletion of Bacteroides and Roseburia. Functional analysis revealed significant downregulation of metabolic pathways, including arginine biosynthesis, alanine, aspartate, and glutamate metabolism. Plasma metabolomics identified reduced arginine levels and disruptions in key amino acid and energy metabolism pathways, suggesting systemic arginine depletion. Proteomic analysis further demonstrated down-regulation of folate hydrolase 1 (FOLH1), a key enzyme in glutamate metabolism, implicating metabolic dysregulation in TCP pathogenesis.

Conclusion: The depletion of arginine and associated metabolic disruptions are associated with ICIs-TCP and may represent a potential therapeutic target for mitigating TCP risk in patients receiving ICIs.

Background: Serplulimab is an immune checkpoint inhibitor (ICI) that blocks inhibitors, augmenting anti-tumor immunity but also carrying risks of immune-related adverse events (irAEs). While neuromuscular and cardiac toxicities are rare, their co-occurrence can lead to high mortality. In this article, we report a patient with multiorgan irAEs after treatment with chemoimmunotherapy.

Case presentation: A 49-year-old man with lung adenocarcinoma developed thyroid dysfunction 3 weeks after initial chemoimmunotherapy (carboplatin, pemetrexed, serplulimab). Following the second cycle, he presented with speech difficulty, bilateral ptosis, dysphagia, fatigue, and elevated creatine kinase (2112 U/L) and troponin T (570 ng/L), suggesting ICI-induced thyroid dysfunction, myocarditis, myositis, and myasthenia gravis overlap syndrome. Brain magnetic resonance imaging was negative. He received methylprednisolone with initial improvement, but troponin elevation recurred after premature steroid discontinuation. Successful treatment was achieved with high-dose methylprednisolone and intravenous immunoglobulin, leading to normalized cardiac markers.

Conclusions: The serplulimab-induced multiorgan irAEs necessitates enhanced monitoring, biomarker research, and multidisciplinary collaboration to optimize safety and antitumor efficacy.