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Colon adenocarcinoma (COAD) is one of the leading causes of cancer-associated deaths worldwide. Patients with microsatellite instability-high (MSI-H) tumors were shown to highly benefit from immune checkpoint inhibitors (ICIs) than patients with microsatellite stable (MSS) tumors. Furthermore, the infiltration of immune cells and the expression of cancer stem cells (CSCs) in COAD were associated with the anti-tumor immune response. However, the potential mechanisms showing the relationship between microsatellite instability and CSCs or tumor-infiltrating immune cells (TIICs) have not been elucidated. Accumulating evidence reveals that achaete-scute family bHLH transcription factor 2 (ASCL2) plays a crucial role in the initiation and progression of COAD and drug resistance. However, the specific biological functions of ASCL2 in COAD remain unknown. In this study, we performed weighted gene co-expression network analysis (WGCNA) between MSS and MSI-H subsets of COAD. The results revealed that ASCL2 was a potential key candidate in COAD. Subsequently, the single-cell RNA-seq revealed that ASCL2 was positively associated with CSCs. Further, ASCL2 was shown to indirectly affect tumor immune cell infiltration by negatively regulating the expression of DUSP4. Finally, we inferred that the immunotherapy-sensitive role of ASCL2/DUSP4 axis on COAD is partly attributed to the activation of WNT/β-catenin pathway. In conclusion, this study revealed that ASCL2 was positively correlated to CSCs and tumor immune infiltration in COAD. Therefore, ASCL2 is a promising predictor of clinical responsiveness to anti-PD-1/PD-L1 therapy in COAD. [ABSTRACT FROM AUTHOR]

While cancer is often related to hyperfibrinogenemia, it is rarely related to hypofibrinogenemia. Specifically, gastric cancer concomitant with unprovoked hypofibrinogenemia and the corresponding treatment approach have been rarely reported. We presented a case of gastric cancer in a 78-year-old Chinese woman in whom sudden, unprovoked refractory hypofibrinogenemia had been found during the whole brain radiotherapy despite stable clinical condition. Fibrinogen supplementation was not useful for controlling her level of fibrinogen. However, when she received sintilimab, an immunotherapy drug acting as programmed death receptor 1 inhibitor, to treat her gastric cancer, fibrinogen rose to the normal level. We also reviewed the literature to explore the causes of hypofibrinogenemia in tumor patients. This case suggests that we need to pay attention to tumor-related coagulation disorders, and monitoring coagulation indicators is essential. Treating primary disease by immunotherapy drugs may be an important method to improve the level of coagulation factors. This is the first report of sintilimab reversing a rare refractory hypofibrinogenemia in a patient with gastric cancer. [ABSTRACT FROM AUTHOR]

Abstract: Hematological malignancies remain incurable diseases because of the high risk of relapse, even after complete remission. Adoptive T-cell therapy (ACT) using modified T cells with chimeric antigen receptors (CARs) targeted to specific tumor-associated antigens expressed by B-cell malignancies represents an attractive approach for cancer immunotherapy. Investigators optimized the design of CARs to enhance receptor mediated T cell signaling and demonstrated that second and third generation CARs, including various costimulatory molecules, resulted in enhanced T-cell persistence and sustained antitumor activity in both in vitro and in vivo mouse models as well as clinical trials. We highlight advances in the use of CARs in the treatment of B-cell malignancies and future challenges in the use of adoptive therapy with CAR-engineered T cells. [Copyright &y& Elsevier]