Immune checkpoint inhibitors are transforming the way cancer is treated. However, these therapies do not benefit all patients and frequently cause significant immune-related adverse events. Biomarkers that identify patients with a favorable early response to therapy are essential for guiding treatment decisions and improving patient outcomes. In this report of our study, we present evidence that shortly after administration of dual PD-1/CTLA-4 blockade, the proinflammatory capacity of peripheral lymphocytes is predictive of tumor progression and survival outcomes in multiple murine models. Specifically, we observed that the quantity of interferon-g (IFNg) produced by peripheral lymphocytes in response to CD3/CD28 stimulation was robustly correlated with subsequent survival outcomes. In the tumor models and early time points assessed in this study, this relationship was considerably more predictive than a host of other potential biomarkers, several of which have been previously reported. Overall, these findings suggest that measuring the capacity of peripheral lymphocytes to produce IFNg may help identify which patients are benefitting from combination anti-PD-1/anti-CTLA-4 immunotherapy.

Background Diabetes mellitus (DM) increases the risk for carpal tunnel syndrome (CTS) and is associated with its own neuropathic complications. Diabetic peripheral neuropathy (DPN) is a common complication seen in diabetic patients. In this study, we examine the relationship between the severity of DPN and CTS. Methods Type 2 diabetic and control patients (n = 292) were recruited at a clinic visit. The Michigan Neuropathy Screening Instrument (MNSI) questionnaire was used to collect data related to peripheral neuropathy. The MNSI scores were compared for patients with CTS with and without DM in univariable and multivariable analyses. χ2 analyses were performed to quantitatively measure the associations between peripheral neuropathy and the presence of CTS. Results Of the 292 patients, 41 had CTS, and 19 of these had both CTS and DM. Of the 138 diabetic patients, 85 had peripheral neuropathy. There was no association between a diagnosis of CTS and an MNSI score indicative of peripheral neuropathy. In the diabetic population, CTS was inversely associated with DPN ( P = .017). The MNSI scores between diabetic and control patients with CTS were comparable. Conclusion The severity of peripheral neuropathy in diabetic patients with and without CTS is comparable. Diabetic patients without peripheral neuropathy have an association with higher incidence of CTS in this study, suggesting that there are disparate mechanisms causing DPN and CTS. Nevertheless, diabetes and CTS are risk factors for developing the other, and future studies should further explore how DPN and CTS differ to tailor patient interventions based on their comorbidities.

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