Immune-checkpoint inhibitors (ICIs) have been proven to have great efficacy in non-small cell lung cancer (NSCLC) as single agents or in combination therapy, being capable to induce deep and durable remission. However, severe adverse events may occur and about 40% of patients do not benefit from the treatment. Predictive factors of response to ICIs are needed in order to customize treatment. The aim of this study is to evaluate the correlation between quantitative positron emission tomography (PET) parameters defined before starting ICI therapy and responses to treatment and patient outcome. We retrospectively analyzed 92 NSCLC patients treated with nivolumab, pembrolizumab or atezolizumab. Basal PET/computed tomography (CT) scan parameters (whole-body metabolic tumor volume—wMTV, total lesion glycolysis—wTLG, higher standardized uptake volume maximum and mean—SUVmax and SUVmean) were calculated for each patient and correlated with outcomes. Patients who achieved disease control (complete response + partial response + stable disease) had significantly lower MTV median values than patients who had not (progressive disease) (77 vs. 160.2, p = 0.039). Furthermore, patients with MTV and TLG values lower than the median values had improved OS compared to patients with higher MTV and TLG (p = 0.03 and 0.05, respectively). No relation was found between the other parameters and outcome. In conclusion, baseline metabolic tumor burden, measured with MTV, might be an independent predictor of treatment response to ICI and a prognostic biomarker in NSCLC patients.

Transient partial remission, a period of low insulin requirement experienced by most patients soon after diagnosis, has been associated with mechanisms of immune regulation. A better understanding of such natural mechanisms of immune regulation might identify new targets for immunotherapies that reverse type 1 diabetes (T1D). In this study, using Cox model multivariate analysis, we validated our previous findings that patients with the highest frequency of CD4 ⁺ CD25 ⁺ CD127 ^hi (127-hi) cells at diagnosis experience the longest partial remission, and we showed that the 127-hi cell population is a mix of Th1- and Th2-type cells, with a significant bias toward antiinflammatory Th2-type cells. In addition, we extended these findings to show that patients with the highest frequency of 127-hi cells at diagnosis were significantly more likely to maintain β cell function. Moreover, in patients treated with alefacept in the T1DAL clinical trial, the probability of responding favorably to the antiinflammatory drug was significantly higher in those with a higher frequency of 127-hi cells at diagnosis than those with a lower 127-hi cell frequency. These data are consistent with the hypothesis that 127-hi cells maintain an antiinflammatory environment that is permissive for partial remission, β cell survival, and response to antiinflammatory immunotherapy.