Targeting the immune checkpoint B7-H3 for next-generation cancer immunotherapy.

Immune checkpoint inhibitors (ICIs) for programmed death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) have become preferred treatment strategies for several advanced cancers. However, response rates for these treatments are limited, which encourages the search for new ICI candidates. Recent reports have underscored significant roles of B7 homolog 3 protein (B7-H3) in tumor immunity and disease progression. While its multifaceted roles are being elucidated, B7-H3 has already entered clinical trials as a therapeutic target. In this review, we overview the recent results of clinical trials evaluating the antitumor activity and safety of B7-H3 targeting drugs. On this basis, we also discuss the challenges and opportunities arising from the application of these drugs. Finally, we point out current gaps to address in the understanding of B7-H3 function and regulation in order to fully unleash the future clinical utility of B7-H3-based therapies for the treatment of cancer.

TM-Score predicts immunotherapy efficacy and improves the performance of the machine learning prognostic model in gastric cancer.

Immunotherapy is becoming increasingly important, but the overall response rate is relatively low in the treatment of gastric cancer (GC). The application of tumor mutational burden (TMB) in predicting immunotherapy efficacy in GC patients is limited and controversial, emphasizing the importance of optimizing TMB-based patient selection. By combining TMB and major histocompatibility complex (MHC) related hub genes, we established a novel TM-Score. This score showed superior performance for immunotherapeutic selection (AUC = 0.808) compared to TMB, MSI status, and EBV status. Additionally, it predicted the prognosis of GC patients. Subsequently, a machine learning model adjusted by the TM-Score further improved the accuracy of survival prediction (AUC > 0.8). Meanwhile, we found that GC patients with low TM-Score had a higher mutation frequency, higher expression of HLA genes and immune checkpoint genes, and higher infiltration of CD8+ T cells, CD4+ helper T cells, and M1 macrophages. This suggests that TM-Score is significantly associated with tumor immunogenicity and tumor immune environment. Notably, based on the RNA-seq and scRNA-seq, it was found that AKAP5, a key component gene of TM-Score, is involved in anti-tumor immunity by promoting the infiltration of CD4+ T cells, NK cells, and myeloid cells. Additionally, siAKAP5 significantly reduced MHC-II mRNA expression in the GC cell line. In addition, our immunohistochemistry assays confirmed a positive correlation between AKAP5 and human leukocyte antigen (HLA) expression. Furthermore, AKAP5 levels were higher in patients with longer survival and those who responded to immunotherapy in GC, indicating its potential value in predicting prognosis and immunotherapy outcomes. In conclusion, TM-Score, as an optimization of TMB, is a more precise biomarker for predicting the immunotherapy efficacy of the GC population. Additionally, AKAP5 shows promise as a therapeutic target for GC.

Rare pulmonary embolism in a pregnant patient: A primary diffused pulmonary artery myxofibrosarcoma case report.

A 37-year-old female patient presented with shortness of breath, cough, and chest pain complaints from the 12th week of her first pregnancy. At the 28th week, labor induction had to be performed because of severe dyspnea and hyoxemia. Thereafter, a diffused pulmonary embolism was detected by echocardiography and CT angiography, without histological diagnosis. Pulmonary endarterectomy was performed, and it was found during operation that a huge, lobular mass originated in the posterior wall and extended throughout the vasculature of both lungs, and a mucinous pellicle covered the entire pulmonary endothelium. Pathology revealed a low-grade myxofibrosarcoma with positive vimentin and SMA, partially positive CD-34.

A Prognostic Nomogram of Colon Cancer With Liver Metastasis: A Study of the US SEER Database and a Chinese Cohort.

BACKGROUND: Among colon cancer patients, liver metastasis is a commonly deadly phenomenon, but there are few prognostic models for these patients. METHODS: The clinicopathologic data of colon cancer with liver metastasis (CCLM) patients were downloaded from the Surveillance, Epidemiology and End Results (SEER) database. All patients were randomly divided into training and internal validation sets based on the ratio of 7:3. A prognostic nomogram was established with Cox analysis in the training set, which was validated by two independent validation sets. RESULTS: A total of 5,700 CCLM patients were included. Age, race, tumor size, tumor site, histological type, grade, AJCC N status, carcinoembryonic antigen (CEA), lung metastasis, bone metastasis, surgery, and chemotherapy were independently associated with the overall survival (OS) of CCLM in the training set, which were used to establish a nomogram. The AUCs of 1-, 2- and 3-year were higher than or equal to 0.700 in the training, internal validation, and external validation sets, indicating the favorable effects of our nomogram. Besides, whether in overall or subgroup analysis, the risk score calculated by this nomogram can divide CCLM patients into high-, middle- and low-risk groups, which suggested that the nomogram can significantly determine patients with different prognosis and is suitable for different patients. CONCLUSION: Higher age, the race of black, larger tumor size, higher grade, histological type of mucinous adenocarcinoma and signet ring cell carcinoma, higher N stage, RCC, lung metastasis, bone metastasis, without surgery, without chemotherapy, and elevated CEA were independently associated with poor prognosis of CCLM patients. A nomogram incorporating the above variables could accurately predict the prognosis of CCLM.