Background Anti-PD-1 monoclonal antibody, nivolumab, has shown efficacy for advanced gastric cancer (AGC). However, the specific immune cell subsets predominantly activated during the period of anti-PD-1 therapy for AGC have not been clarified. Methods Peripheral blood of 30 AGC patients treated with nivolumab was prospectively obtained before the initial and second administrations and at the time of progressive disease (PD). The proportions of immune cell subsets and the serum concentrations of cytokines were systematically analysed by flow cytometry. Associations of subsets and serum cytokines with therapeutic effects were evaluated. Results After the initial administration, significant increases in activated central/effector memory, activated effector T cells, and activated T-helper 1 subsets were observed. At the time of PD, activated regulatory T cells, LAG3-positive CD4+/CD8+ T cells, and TIM3-positive CD4+/CD8+ T cells increased significantly. Significant positive correlations were shown between progression-free survival and proportions of LAG3-positive CD4+/CD8+ T cells and of OX40-positive CD4+/CD8+ T cells (log-rank p = 0.0008, 0.0003, 0.0035 and 0.0040). Conclusions Nivolumab therapy enhances activation of central/effector memory and effector subsets of CD4+/CD8+ T cells. The expression levels of LAG-3 and OX40 on T cells correlated with the efficacy of nivolumab therapy and could be reasonable biomarkers for anti-PD-1 therapy.

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Although the neutrophil to lymphocyte ratio (NLR) was reported to be a predictive biomarker for clinical outcomes in various types of cancer, including recurrent or metastatic head and neck cancer (R/M HNSCC) treated with nivolumab, the usefulness of the pretreatment C-reactive protein/albumin ratio (CAR) as a prognostic marker remains to be clarified. This study aimed to analyze the clinical usability of the CAR in comparison with that of the NLR. 46 R/M HNSCC patients treated with nivolumab were retrospectively analyzed. The optimal cutoff value for the CAR was calculated using receiver operating characteristic curve analysis. The optimal cutoff value for the CAR was set to 0.30. On multivariate analyses, a high CAR was significantly associated with poor overall survival (adjusted HR, 2.19; 95% CI, 1.42–3.47; p < 0.01) and progression-free survival (adjusted HR, 1.98; 95% CI, 1.38–2.80; p < 0.01). The overall response rate and disease control rate for the high CAR patients were lower than for the low CAR patients. The CAR had significantly higher area under the curve values than the NLR at 2 and 4 months. The pretreatment CAR might be an independent marker for prognosis and efficacy in R/M HNSCC patients treated with nivolumab.

To investigate the process of homeothermal acclimation to extrauterine environment, core and peripheral body temperatures in the human neonate were continuously and simultaneously recorded. Twenty-one term-delivered babies were divided into two groups. In group I, 10 babies were kept at 32–34 °C for the first 2 h of extrauterine life and at 24–26 °C for the succeeding 6 h. In group II, 11 were kept at 24–26 °C for the first 8 h after delivery. Three thermisters were used: one catheter-type placed in the rectum and two involving the zero-heat flow method placed at the sternum and footsole. Because of technical limitations, rectal temperature (Tre) was monitored until temperature in the sternum (Tst) stabilized, after which this transition from Tre to Tst was noted as Tre-st. Changes in resulting temperatures were quantitatively analyzed using Student’s t test, for both intra- and intergroup comparisons. Tre-st significantly decreased during the first 28 and 42 min for groups I and II, respectively, after which time this temperature rose and stabilized. In group I, the Tre-st reached the homeothermal stage at 2 h 49 min, while 4 h 27 min were required for group II. In group I, the footsole temperature (Tsf) reached a plateau after 2 h 10 min. In group II, Tsf showed a large decrease followed by a slow rise, with no stability achieved during the 8-hour observation period. Intergroup comparisons revealed that the mean Tsf reached conditions not significantly different from those of group I at 6 h 57 min. From the differences in changes seen in the patterns of body temperature distribution, neonates show different courses of homeothermal acclimation to extrauterine life, depending on the ambient temperature to which they are initially exposed.

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