Background/Aim: Cancer immune therapy by immune checkpoint inhibitors (ICIs) is a promising therapeutic strategy for various cancer types. Among ICIs, anti-programmed cell death protein-1 (PD1) and antiprogrammed death-ligand 1 (PD-L1) antibodies have shown a remarkable clinical benefit. The present study aimed to address the functional and clinical significance of serum levels of soluble PD-L1 (sPD-L1) in patients. Materials and Methods: A total of 21 patients, 11 with NSCLC, nine with gastric cancer and one with bladder cancer, who underwent anti-PD-1 therapy were evaluated for sPD-L1 concentration by ELISA analyses at diagnosis and after treatment. Results: Pretreatment levels of sPD-L1 in patients who received ICIs were not remarkably correlated with the overall survival of these patients (r=0.3394, p=0.1323). Reduction of plasma sPD-L1 level was significantly correlated with tumor regression in patients administered four cycles of treatment (p<0.05). Conclusion: sPD-L1 might be derived and secreted from tumors and might be useful to identify primary responders to ICIs at a relatively early treatment timepoint.Programmed death protein (PD1) and its ligand PD-L1 are central components in immune suppression, comprising the so-called 'immune checkpoint' (1, 2). Accumulating evidence revealed that the PD1/PD-L1 pathway is closely involved in resistance to antitumor immunity in multiple cancer types. Therefore, targeting immune checkpoints using immune checkpoint inhibitors (ICIs), such as those against PD1/PD-L1, has contributed to recent advances in cancer therapeutics (3, 4). However, many patients failed to respond or developed resistance after an initial response to ICIs. Predictive biomarkers for identifying potential responders to ICIs are currently under debate (5). Notably, several lines of evidence suggest a correlation between tumor PD-L1 expression and response to ICIs in variable malignancies including lung adenocarcinoma, melanoma, refractory Hodgkin's lymphoma, and other solid tumor types (6-10). Intriguingly, such correlation was reported for the expression level of membrane-bound PD-L1 (mPD-L1) on tumor tissues and plasma level of soluble PD-L1 (sPD-L1) in the blood of patients with cancer, highlighting the importance of their prognostic value. Several studies showed that high expression of sPD-L1 was associated with a poor prognosis in multiple types of malignant tumor. This suggests that sPD-L1 might be a predictive marker for low treatment responses to conventional chemotherapy and patients with high expression of sPD-L1 might be suitable for ICI therapy (11)(12)(13)(14)(15)(16)(17)(18)(19)(20). However, it remains unclear whether the plasma sPD-L1 level is derived from malignant tumors pre-existing in patients and reflects a potential response to ICIs. Here, we measured the plasma level of sPD-L1 collected from patients with non-small cell lung cancer (NSCLC) and those with gastric cancer who underwent anti-PD1 therapy and analyzed 5195

Immune checkpoint inhibitors (ICIs) confer remarkable therapeutic benefits to patients with various cancers. However, many patients are non-responders or develop resistance following an initial response to ICIs. There are no reliable biomarkers to predict the therapeutic effect of ICIs. Therefore, this study investigated the clinical implications of plasma levels of soluble anti-programmed death-1 (sPD-1) in patients with cancer treated with ICIs. In total, 22 patients (13 with non-small-cell lung carcinoma, 8 with gastric cancer, and 1 with bladder cancer) were evaluated for sPD-1 concentration using enzyme-linked immunosorbent assays for diagnostic and anti-PD-1 antibody analyses. sPD-1 levels were low before the administration of anti-PD-1 antibodies. After two and four cycles of anti-PD-1 antibody therapy, sPD-1 levels significantly increased compared with pretreatment levels (p = 0.0348 vs. 0.0232). We observed an increased rate of change in plasma sPD-1 concentrations after two and four cycles of anti-PD-1 antibody therapy that significantly correlated with tumor size progression (p = 0.024). sPD-1 may be involved in resistance to anti-PD-1 antibody therapy, suggesting that changes in sPD-1 levels can identify primary ICI non-responders early in treatment. Detailed analysis of each cancer type revealed the potential of sPD-1 as a predictive biomarker of response to ICI treatment in patients with cancer.

Objectives The relationship between eosinophils and cancer prognosis is unknown. Therefore, we analyzed the relationship between circulating eosinophils and the survival of stage IIA and IIB pancreatic cancer patients who underwent surgical resection. Methods This study included a retrospective cohort of 67 consecutive patients. Patients were categorized into two different groups based on the optimal cutoff for pretreatment levels of each biomarker, according to the receiver operating characteristic curves. Results The Kaplan-Meier method showed that low eosinophil (P = 0.0403), high neutrophil (P = 0.0066), and high monocyte (P = 0.0003) counts were associated with short overall survival (OS). Low lymphocyte-to-monocyte ratio (P = 0.0194) and eosinophil-to-lymphocyte ratio (ELR) (P = 0.0413) were associated with reduced OS. In multivariate analysis, histological differentiation (P = 0.0014), high neutrophils (P = 0.047), high monocytes (P = 0.029), and low eosinophils (P < 0.0001) were correlated with poorer OS. Histological differentiation (P = 0.033), low lymphocyte-to-monocyte ratio (P = 0.029), and low ELR (P = 0.005) were correlated with poor OS and were significant independent prognostic factors of poor outcomes. Conclusions Low eosinophils and low ELR were significant independent prognostic factors of poor outcomes.

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Background/Aim: There is an increasing use of immunotherapy for non-small cell lung cancer (NSCLC) patients. The present study analysed the effect of antibiotic use on the outcome of NSCLC patients undergoing treatment with anti-programmed cell death-1 (anti-PD-1) immunotherapy. Patients and Methods: This was a retrospective study of 69 NSCLC patients. Eighteen out of 69 patients received antibiotics within 21 days before or within 21 days after start of anti-PD-1 therapy. Results: Patients treated with anti-PD-1 antibodies receiving antibiotics had greatly decreased objective response rate (ORR), overall survival (OS) and progression-free survival (PFS) compared to those who did not use antibiotics. Multivariate analysis showed that antibiotic treatment of patients on anti-PD-1 antibody therapy was an independent negative predictive factor of PFS; however, it was not a significant independent predictive factor of OS. Conclusion: Use of antibiotics within 21 days before and after anti-PD-1 treatment initiation in patients with NSCLC strongly reduced OS and PFS, suggesting the two treatments should not be combined.Immunotherapy with anti-programmed cell death-1 (anti-PD-1) antibody has been only modestly successful in non-small cell lung cancer (NSCLC) (1). Thus, there is a critical need to identify more effective treatment strategies for anti PD-1 treatment of NSCLC.Specific intestinal bacteria have been reported to affect the immune system and therapeutic outcome of anti-PD-1 immunotherapy in NSCLC, melanoma, renal cell carcinoma (RCC) and urothelial carcinoma (UC) (2-5). Additionally, the diversity of bacterial flora may also affect the therapeutic outcome of anti-PD-1 immunotherapy (6).