AML cell-derived exosomes suppress the activation and cytotoxicity of NK cells in AML via PD-1/PD-L1 pathway.

Exosomes are bilayer lipid bodies and contain a variety of bioactive molecules such as proteins, lipids, and nucleic acids, and so forth. Exosomes derived from solid tumors may play critical roles in tumor development and immune evasion. However, the underlying effects of tumor-derived exosomes on immune function in modulating intercellular crosstalk within the bone marrow niche during acute myeloid leukemia (AML) development and immune evasion remain largely elusive. In this study, we aimed to explore the role of AML-exos in AML immune evasion. First, we isolated tumor-derived exosomes from AML cells (AML-exos) and revealed the presence of programmed cell death ligand-1 (PD-L1) protein in AML-exos. Next, we demonstrated that AML-exos can directly suppress the activation of natural killer (NK) cells and inhibit the cytotoxicity of NK cells, probably through activating the programmed cell death-1 (PD-1)/PD-L1 pathway. Furthermore, the inhibitory effect of AML-exos on NK cells could be alleviated by either PD-L1 inhibitor or antagonist. In summary, we demonstrated that AML-exos possess a PD-L1-dependent tumor-promoting effect which may contribute to immune tolerance in antitumor therapy, but blocking the PD-1/PD-L1 pathway may alleviate the tumor immunosuppression induced by AML-exos. Our findings in this study may offer a new immunotherapy strategy to cure AML.

Endometrial cancer intraoperative sentinel lymph node identification can effectively guide treatment.

OBJECTIVE: To explore the significance of intraoperative sentinel lymph node (SLN) identification in endometrial cancer. METHODS: We retrospectively analyzed the clinical data of 56 patients with intraoperative SLN recognition (group A) and 50 patients without intraoperative SLN recognition (group B). SLN and pelvic abdominal lymph node distribution, SLN recognition rate, SLN recognition effect, mortality, the incidence of adverse events, and cumulative survival rate were statistically analyzed. RESULTS: SLN were identified and removed in 41 of the 56 patients, with a recognition rate of 82.14% (46/56). The sensitivity of SLN was 83.72%, the specificity was 84.62%, and the negative predictive value was 61.11%. There were 15 patients with no SLN metastasis found in the pathological examination during the operation, among which two patients with poorly differentiated adenocarcinoma and clinical stage II patients underwent immunohistochemical staining, and three patients showed SLN micro-metastasis but no cancer tissue metastasis in the lymph node dissection. There was no significant difference in the incidence of total adverse events between group A and group B (P>0.05). The cumulative survival rate of group A was higher than that of group B (P=0.018). CONCLUSION: Intraoperative SLE identification can avoid false negative results, is safe and feasible, and can prolong the survival time of patients with endometrial cancer.