Integrin αvß6 mediates the immune escape through regulation of PD-L1 and serves as a novel marker for immunotherapy of colon carcinoma.

The immune escape of colon cancer and its role in the response to immunotherapies such as PD-1/PD-L1 checkpoint inhibitors have long been of great interest. The positive outcomes of immunotherapy are limited by the immunosuppressive nature of the tumor microenvironment. Integrin αvß6, which can regulate the progression of colon cancer, was recently reported to be involved in the immune suppression of colon cancer. In the present study, we explored the correlation between αvß6 and PD-L1 expression by immunohistochemistry of colon cancer tissues. Then, the regulation of PD-L1 signaling by αvß6 in colon cancer cells was demonstrated. We constructed an in vivo model and performed immunophenotyping experiments to analyze further the regulation of the immune response by αvß6. The role of αvß6 in the response to anti-PD-1 therapy in colon cancer was also verified. αvß6-positive tissues exhibited increased PD-L1 expression. Inhibition of αvß6 not only downregulated constitutive PD-L1 expression but also decreased IFN-γ-induced PD-L1 expression. In addition, αvß6-induced PD-L1 expression was suppressed by the ERK inhibitor PD98059, and knockdown of the ß6-ERK2 binding site had the equivalent effect. αvß6 decreased CD8+ T cell infiltration and granzyme B expression in CD8+ T cells in colon cancer patients. Furthermore, mice engrafted with αvß6-expressing colon cancer cells exhibited an unsatisfactory response to anti-PD-1 therapy, and anti-PD-1-induced increases in CD4+ and CD8+ T cell infiltration could be inhibited by αvß6. These results indicate that αvß6 mediates immune escape in colon cancer by upregulating PD-L1 through the ERK/MAPK pathway. Moreover, αvß6 could serve as a marker for the efficacy of anti-PD-1 therapy in colon cancer.

Severe Infection Mimicking AML due to Bone Marrow Suppression: a Diagnostic Challenge.

BACKGROUND: Infection may lead to agranulocytosis due to bone marrow suppression. However, a rare case with infection presented with morphological features of acute myeloid leukemia (AML). METHODS: We report a case of extreme agranulocytosis due to severe infection mimicking acute myeloid leukemia. The case was definitively diagnosed by subsequent morphology, flow cytometry, and bone marrow biopsy, and subsequent successful anti-infective treatment confirmed the diagnosis. CONCLUSIONS: To date, no case of a patient diagnosed with severe infection mimicking AML has been reported. The case emphasizes the importance of an integrated diagnostic work-up, especially careful clinical observation and differential diagnosis.

Research Progress on Extracellular Matrix Involved in the Development of Preeclampsia.

Preeclampsia (PE) is a serious pregnancy complication, and its primary clinical manifestations are gestational hypertension and proteinuria. Trophoblasts are responsible for the basic functions of the placenta during placental development; recent studies have revealed that placental "shallow implantation" caused by the decreased invasiveness of placental trophoblasts plays a crucial role in PE pathogenesis. The interaction between the cells and the extracellular matrix (ECM) plays a crucial role in trophoblast proliferation, differentiation, and invasion. Abnormal ECM function can result in insufficient migration and invasion of placental trophoblasts, thus participating in PE. This article summarizes the recent studies on the involvement of ECM components, including small leucine-rich proteoglycans, syndecans, glypicans, laminins, fibronectin, collagen, and hyaluronic acid, in the development of PE. ECM plays various roles in PE development, most notably by controlling the activities of trophoblasts. The ECM is structurally stable and can serve as a biological diagnostic marker and therapeutic target for PE.