Colorectal cancer (CRC) patients, especially those with deficient mismatch repair (dMMR)/microsatellite instability-high (MSI-H) tumors, whose sensitivity to immune checkpoint inhibitors (ICIs) is significantly higher than that of patients with microsatellite-stable (MSS)/microsatellite instability-low (MSI-L) tumors, have derived clinical benefits from immunotherapy. Most studies have not systematically evaluated the immune characteristics and immune microenvironments of MSI-H and MSS/MSI-L CRCs. We analyzed the relationship between the MSI status and prognosis of ICI treatment in an immunotherapy cohort. We further used mutation data for the immunotherapy and The Cancer Genome Atlas (TCGA)-CRC [colon adenocarcinoma (COAD) + rectum adenocarcinoma (READ)] cohorts. For mRNA expression, mutation data analysis of the immune microenvironment and immunogenicity under different MSI statuses was performed. Compared with CRC patients with MSS/MSI-L tumors, those with MSI-H tumors significantly benefited from ICI treatment. MSI-H CRC had more immune cell infiltration, higher expression of immune-related genes, and higher immunogenicity than MSS/MSI-L CRC. The MANTIS score, which is used to predict the MSI status, was positively correlated with immune cells, immune-related genes, and immunogenicity. In addition, subtype analysis showed that COAD and READ might have different immune microenvironments. MSI-H CRC may have an inflammatory tumor microenvironment and increased sensitivity to ICIs. Unlike those of MSI-H READ, the immune characteristics of MSI-H COAD may be consistent with those of MSI-H CRC.
Immunotherapy has been incorporated into the first- and second-line treatment strategies for non-small cell lung cancer (NSCLC), profoundly ushering in a new treatment landscape. However, both adaptive signaling and oncogenic (epidermal growth factor receptor (EGFR)-driven) signaling may induce PD-L1 upregulation in NSCLC. Nevertheless, the superiority of immune checkpoint inhibitors (ICIs) in advanced EGFR-mutant NSCLC is only moderate. ICIs appear to be well tolerated, but clinical activity for some advanced EGFR-mutant NSCLC patients has only been observed in a small proportion of trials. Hence, there are still several open questions about PD-L1 axis inhibitors in patients with NSCLC whose tumors harbor EGFR mutations, such as the effect of EGFR tyrosine kinase inhibitors (TKIs) or EGFR mutations in the tumor microenvironment (TME). Finding the answers to these questions requires ongoing trials and preclinical studies to identify the mechanisms explaining this possible increased susceptibility and to identify prognostic molecular and clinical markers that may predict benefits with PD-1 axis inhibition in this specific NSCLC subpopulation. The presence of multiple mechanisms, including dynamic immune TME profiles, changes in PD-L1 expression and low tumor mutational burdens, may explain the conflicting data regarding the correlation between PD-L1 axis inhibitors and EGFR mutation status. We conducted a review of this currently controversial topic in an attempt to aid in the decision-making process.
BackgroundInsulin resistance (IR) plays a vital role in the pathogenesis of Type 2 Diabetes Mellitus (T2DM). The mechanism of IR may be associated with inflammation, whereas the neutrophil-lymphocyte ratio (NLR) is a new indicator of subclinical inflammation. Scholars have rarely investigated the relationship between IR and NLR. This study aims to evaluate the relationship between IR and NLR, and determine whether or not NLR is a reliable marker for IR.MethodsThe sample consists of a total of 413 patients with T2DM, 310 of whom have a HOMA-IR value of > 2.0. The control group consists of 130 age and BMI matched healthy subjects.ResultsThe NLR values of the diabetic patients were significantly higher than those of the healthy control (P < 0.001), and the NLR values of the patients with a HOMA-IR value of > 2.0 are notably greater than those of the patients with a HOMA-IR value of ≤ 2.0 (P < 0.001). Pearson correlation analysis showed a significant positive correlation of NLR with HOMA-IR (r = 0.285) (P < 0.001). Logistic regression analysis showed that the risk predictors of IR include NLR, TG and HbA1c. NLR (P < 0.001, EXP(B) = 7.231, 95% CI = 4.277–12.223) levels correlated positively with IR. The IR odds ratio increased by a factor of 7.231 (95% CI, 4.277–12.223) for every one unit increase in NLR.ConclusionsIncreased NLR was significantly associated with IR, and high NLR values may be a reliable predictive marker of IR.Electronic supplementary materialThe online version of this article (doi:10.1186/s12902-015-0002-9) contains supplementary material, which is available to authorized users.
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