Infiltration of IL-1β-driven MDSCs was a significant factor in anti-PD-1 resistance in CRC. ConclusionsĬD8 + T cells and IL-1β were identified as the cell type and gene, respectively, with the highest correlation with anti-PD-1 resistance. Experiments with both clinical samples and mice indicated that infiltration of IL-1β-driven MDSCs and inactivation of CD8 + T cells contribute to anti-PD-1 resistance in MSI-H/dMMR CRC. ScRNA-seq analysis showed that, compared with the treatment-resistant group, the treatment-sensitive group accumulated more CD8 + T cells. The objective response rate was 43.48%, and the disease control rate was 69.57%. ![]() Tumor responses in 23 patients with MSI-H/dMMR mCRC were evaluated by radiology. Moreover, quantitative analysis and sorting of myeloid-derived suppressor cells (MDSCs) and CD8 + T cells were performed using flow cytometry. Immunohistochemistry, quantitative real-time PCR, and western blotting were performed to examine the expression of IL-1β and MMP9. Immunohistochemistry and immunofluorescence were applied to verify key genes and cell marker molecules in clinical samples. Then, a protein‒protein interaction network was constructed to identify key genes. To identify the marker genes in each cluster, distinct cell clusters were identified and subjected to subcluster analysis. Cells from primary lesions of patients with MSI-H/dMMR mCRC were analyzed using scRNA-seq. The response of primary and metastatic lesions to first-line anti-PD-1 monotherapy was evaluated by radiology. Resistance-related cell types and genes identified by this analysis were subsequently verified in clinical samples and mouse models to further reveal the molecular mechanism of anti-PD-1 resistance in MSI-H or dMMR mCRC. Thus, we used scRNA-seq to assess differences among microenvironment components between therapy-resistant and therapy-sensitive groups in MSI-H/mismatch repair-deficient (dMMR) mCRC. Single-cell RNA sequencing (scRNA-seq) enables unbiased analysis of the full variety of cells comprising the tumor microenvironment. My Math tutor, Adrian, helped me to an A2.The objective response rate of microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC) patients with first-line anti-programmed cell death protein-1 (PD-1) monotherapy is only 40–45%. ![]() That helped me into and that helped get me into the PFP course of my choice! Tricia Wi, 16 My Math tutor, Adrian, helped me to an A2. My Math tutor, Adrian, helped me improve from a U grade to an A2 and that helped get me into the PFP course of my choice! I highly recommend Elucidation Learning to other parents! Jack Wong, dad of Asher. My son's school results and his attitude towards learning have improved positively. I highly recommend Elucidation Learning to other parents! Lucas, 11 My son's school results and his attitude towards learning have improved positively. Teacher Fira helps me understand the different concepts in Math and Science. ![]() Manfred See, 16 With Mr Lee's help, my Math results have improved from failing to A2s and A1s! Manfred See, 16 fun with them! Teacher Fira helps me understand the different concepts in Math and Science. Mrs Ong, mum of Caryn & Charity, CHIJ With the help from Mr Lee, my Math results have improved a lot, from failing to A2s and even A1s! Mrs Ong, mum of Caryn & Charity, CHIJ My girls joined the Daily Revision Program and the team has nurtured them into confident and resilient individuals. Although Teacher Lena no longer teaches me, she continues to check on me and motivate me Manfred See, 16 fun with them! My girls joined the Daily Revision Program and the team has nurtured them into confident, resilient individuals! We recommend Elucidation Learning highly to all parents! Mrs Yap, parent of Tricia & Sarah, MGS Although Teacher Lena no longer teaches me, she continues to check on me and motivate me to work harder. Mrs Yap, parent of Tricia & Sarah,MGS Both our girls achieved As in their exams. We recommend Elucidation Learning highly to all parents! Both our girls achieved As in their exams.
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