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This prospective study was conducted to identify predictive markers for the response of metastatic renal cell carcinoma (RCC) to tyrosine kinase inhibitors (TKIs). Patients with histologically proven RCC with at least one measurable metastatic lesion were enrolled in this study. Blood samples were collected prior to treatment and the plasma levels of 27 cytokines were measured. Tumor response was assessed 8-12 weeks after the initiation of TKI treatment. A total of 13 patients (11 men and 2 women) with a median age of 63 years received sunitinib (8 cases), sorafenib (1 case), or axitinib (4 cases). Partial response (PR) was achieved in 5 patients (38%), stable disease (SD) in 4 (30%) and progressive disease (PD) was noted in 4 (30%). The plasma granulocyte macrophage colony-stimulating factor (GM-CSF) level in PR cases was significantly higher compared to that in SD or PD cases (P=0.012). Therefore, GM-CSF may be a predictive biomarker of the response of RCC to TKI treatment, suggesting that TKIs may exert clinical effects not only through suppression of the vascular endothelial growth factor, but also through immune system modulation. [ABSTRACT FROM AUTHOR]

Background: Near-infrared photoimmunotherapy (NIR-PIT) for head and neck cancer is a recently developed therapy. However, there is limited data on patients receiving NIR-PIT in real clinical settings. Methods: Seven NIR-PIT sessions were administered to five patients with head and neck squamous cell carcinoma (HNSCC). Serum damage-associated molecular patterns (DAMPs) (HMGB1 and Hsp70 levels), and cytokine and chemokine production, were compared before and after NIR-PIT. Results: The serum concentration of HMGB1 increased after NIR-PIT (p=0.031, Wilcoxon test) in all patients except one who did not achieve a clinical response. Chemokines MIP-1α (CCL3) and MIP-1β (CCL4) increased significantly 1–3days after treatment (CCL3, p=0.0036; CCL4, p=0.0016, Wilcoxon test). A low pretreatment neutrophil-to-lymphocyte ratio (NLR) was associated with a better response to therapy and survival. Conclusions: The release of DAMPs, and cytokine/chemokine production, were detected in the patients' peripheral blood. The baseline NLR may predict patient outcomes in response to NIR-PIT. [ABSTRACT FROM AUTHOR]

Background aims. The outcome for pancreatic cancer after surgery remains highly unsatisfactory, and development of more effective therapies is urgently needed. Therefore, we conducted a phase I clinical study of a novel combination of gemcitabine (GEM) and autologous γδ T-cell therapy for patients with curatively resected pancreatic cancer (University Hospital Medical Information Clinical Trials Registry identifier 000000931). Methods. From July 2008 to December 2012, 56 consenting patients were recruited. After preliminary testing of γδ T-cell proliferative capacity, 28 patients were eligible to receive combined GEM plus γδ T-cell therapy. Results. During treatment, most of the adverse events observed were due to GEM, including myelosuppression and gastrointestinal disorders. No severe adverse events were obviously related to the γδ T-cell therapy. To evaluate clinical efficacy, patients receiving combined therapy (Group A, n = 28) were compared with those receiving GEM alone (Group B, n = 20). No significant differences were observed between the two groups in recurrence-free survival or overall survival. However, we found that, relative to progressing patients, more γδ T-cells were detectable in the blood of recurrence-free patients after only two injections (P < .0388) and more so five injections (P < .0175). Patients with >15% peripheral γδ T-cells after two injections and >20% after five injections had a chance of a more favorable clinical outcome. Accumulation of γδ T cells was positively related to the quality of the infused products, with those having >80% γδ T cells being optimal. Discussion. High quality of the γδ T-cell product is crucial to achieve a high percentage of γδ T cells in the blood and to achieve better clinical outcome. [ABSTRACT FROM AUTHOR]

Heat shock protein 105 (Hsp105) is one of the cancer/testis antigens, which is overexpressed in a variety of cancer cells, including urinary bladder cancer, and has been investigated as a target molecule for immunotherapy due to its immunogenicity. In this study, we assessed the expression of Hsp105 in primary bladder cancer samples from 84 patients treated with radical cystectomy, using immunohistochemical analysis, and investigated its correlation with clinicopathological characteristics and cancer-specific survival. The immunoreactivity of Hsp105 expression was evaluated as a score of 0 3, according to the intensity of the signal. The Hsp105 expression was high (score 2 or 3) in 31 cases and low (score 0or1) in 53cases; however, it was not significantly correlated with age, nuclear grade, pathological tumor stage and previous intravesical Bacillus Calmette-Guérin immunotherapy. Female gender, lymphovascular invasion and lymph node metastasis were associated with low Hsp105 scores, although the differences were not statistically significant (P=0.071, 0.061 and 0.175, respectively). However, a high Hsp105 score was significantly associated with a favorable prognosis (P=0.017) and was identified as an independent prognostic factor by multivariate analysis (P=0.032; hazard ratio, 2.34). These findings suggested that the expression of Hsp105 may be a novel indicator of a favorable prognosis in bladder cancer. [ABSTRACT FROM AUTHOR]