Many patients are not diagnosed until they are already in advanced stages of disease, which is a significant obstacle to effective treatment. Although diagnosis and treatment strategies for CRC have improved rapidly in recent years, the prognosis is unfavorable for many CRC patients. IL-1β antagonists are expected to be developed as a new treatment for anti-PD-1 inhibitor resistance.Ĭolorectal cancer (CRC) is one of the most common malignant digestive tract tumors and has the second highest mortality rate and the third highest incidence rate among all malignant tumors. 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. Synonyms for explains include shows, teaches, coaches, demonstrates, educates, instructs, trains, tutors, advises and counsels.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%. Synonyms for Explain (other words and phrases for Explain). Details of Explain synonyms, explain antonyms – ĥ0 synonyms for explain: make clear or plain, describe, demonstrate, illustrate, teach, define, solve. Synonyms for EXPLAIN: explicate, construe, interpret, expound, elucidate, decipher, describe, clarify, make clear Antonyms for EXPLAIN: confuse, puzzle, obscure, be. Synonyms for EXPLAINED: confirmed, determined, established, corroborated, convincing, validated, substantiated, plausible Antonyms of EXPLAINED: inexplicable. More info about explain – Cambridge English Thesaurus with synonyms andĮxplain – Synonyms, related words and examples | Cambridge English Thesaurus. Synonyms for explain include clarify, describe, define, demonstrate, detail, elucidate, illustrate, disclose, make clear and point out. People Also Read: Olivia Farmer Looking For Love On "Wants A Wife"
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