Sequential severe immune-related adverse events induced by PD-1 inhibitor: a case report and literature review.

In a variety of cancers, immune checkpoint inhibitors (ICIs) have demonstrated substantial survival advantages. Nevertheless, the widespread use of ICIs in the clinic has resulted in a growing interest in immune-related adverse events (irAEs) and their treatment methods. This paper reports a case in which a patient with three sequential severe irAEs was successfully treated. After undergoing two regimens of sintilimab in conjunction with chemotherapy for advanced lung cancer, the patient developed myocarditis combined with hepatitis. Subsequently, the patient developed pneumonia following remission from treatment. We also discuss the mechanism of irAEs, principles of treatment, and progress in the study of biomarkers for early prediction of irAEs by reviewing the literature.

The proportion of tumour stroma predicts response to treatment of immune checkpoint inhibitor in combination with chemotherapy in patients with stage IIIB-IV non-small cell lung cancer.

AIMS: Immunotherapy has brought a new era to cancer treatment, yet we lack dependable predictors for its effectiveness. This study explores the predictive significance of intratumour stroma proportion (iTSP) for treatment success and prognosis in non-small cell lung cancer (NSCLC) patients undergoing treatment with immune check-point inhibitors (ICIs) together with chemotherapy. METHODS AND RESULTS: We retrospectively collected data from patients with unresectable stage IIIB-IV NSCLC who were treated with first-line ICIs and chemotherapy. Each patient received a confirmed pathological diagnosis, and the pathologist evaluated the iTSP on haematoxylin and eosin (H&E)-stained sections of diagnostic tissue slides. Among the 102 H&E-stained biopsy samples, 61 (59.8%) were categorised as stroma-L (less than 50% iTSP), while 41 (40.2%) were classified as stroma-H (more than 50% iTSP). We observed that the stroma-L group exhibited a significantly better objective response rate (ORR) (72.1 versus 51.2%, P = 0.031) and deeper response depth (DpR) (-50.49 ± 28.79% versus -35.83 ± 29.91%, P = 0.015) compared to the stroma-H group. Furthermore, the stroma-L group showed longer median progression-free survival (PFS) (9.6 versus 6.0 months, P = 0.011) and overall survival (OS) (24.0 versus 12.2 months, P = 0.001) compared to the stroma-H group. Multivariate Cox proportional hazards regression analysis indicated that iTSP was a highly significant prognostic factor for both PFS [hazard ratio (HR) = 1.713; P = 0.030] and OS (HR = 2.225; P = 0.003). CONCLUSION: Our findings indicate that a lower iTSP corresponds to improved clinical outcomes and greater DpR in individuals with stage IIIB-IV NSCLC treated with first-line ICIs and chemotherapy. The iTSP could potentially serve as a predictive biomarker for ICIs therapy response.

AHSA1 Regulates Hepatocellular Carcinoma Progression via the TGF-ß/Akt-Cyclin D1/CDK6 Pathway.

Background: Activator of heat shock protein 90 (HSP90) ATPase Activity 1 (AHSA1) regulates proliferation, apoptosis, migration, and invasion of osteosarcoma and hepatocellular carcinoma (HCC). However, the novel mechanism of AHSA1 in the tumor biology of hepatocellular carcinoma (HCC) remains unclear. Methods: We analyzed AHSA1 expression in 85 pairs of clinical samples of HCC and the Cancer Genome Atlas database. The role of AHSA1 in HCC was proved by cell proliferation, colony formation, migration, cell cycle analysis in vitro, xenograft models and tumor metastasis assay in vivo, and bioinformatics. Results: High AHSA1 expression was demonstrated in HCC and associated with invasive depth, clinical stage, and poor overall survival of patients. Univariate Cox analysis confirmed that AHSA1 was an independent prognostic factor for patients with HCC. Meanwhile, AHSA1 upregulation promoted cell proliferation, colony formation, and cell migration in vitro and tumor cell proliferation and metastasis of HCC cells in vivo. AHSA1 upregulation increased the cell cycle transition from G1 to S phase by increasing the expression of cyclinD1, cyclinD3, and cyclin-dependent kinase 6(CD). Transforming growth factor beta 1 (TGF-ß1)-induced protein kinase B (Akt) signaling regulated the expression of downstream targets, including cyclinD1. AHSA1 expression was closely correlated with the expression of TGF-ß, Akt, cyclinD1, cyclinD3, and CDK6 using the Gene Expression Profiling Interactive Analysis database. AHSA1 upregulation participated in HCC progression by regulating TGF-ß/Akt-cyclinD1/CDK6 signaling. Conclusion: AHSA1 might serve as a biomarker for predicting the clinical outcome of patients with HCC. It is vital in tumor metastasis and disease progression of HCC and may facilitate the development of clinical intervention strategies against HCC.

Anlotinib combined with pembrolizumab as first-line treatment for advanced pulmonary sarcomatoid carcinoma: a case report and literature review.

Pulmonary sarcomatoid carcinoma (PSC) is an uncommon variant of non-small cell lung cancer (NSCLC), known for its unfavorable prognosis. Previous studies have elucidated that PSC generally exhibits a significant expression of programmed death-ligand 1 (PD-L1), an elevated tumor mutation burden, and marked vascular invasion. These factors imply the possible effectiveness of treatments like immunotherapy and anti-angiogenic therapy. The subject of this case was a 65-year-old male diagnosed with advanced PSC, characterized by high PD-L1 expression and devoid of known driver gene mutations. Owing to the restrictions imposed by the COVID-19 pandemic, the patient initially underwent home-based treatment with anlotinib, which led to symptomatic improvement after a single treatment cycle. Subsequent hospitalization allowed for the administration of anlotinib plus Pembrolizumab, resulting in a partial response. Radiotherapy was necessitated due to local disease progression. But after 15 cycles of treatment with Pembrolizumab, hyperprogression was observed. The patient's overall survival spanned 14 months, with no evident adverse reactions to the medications. Genomic analysis revealed potential associations between treatment efficacy and mutations in the TP53, NF1, and MET genes. This case underscores the effectiveness and safety of a first-line treatment regimen combining pan-target anti-angiogenic therapy (anlotinib) with anti-tumor immunotherapy.