Lingdi Zhao

Association of myeloid-derived suppressor cells and efficacy of cytokine-induced killer cell immunotherapy in metastatic renal cell carcinoma patients.

Metastatic renal cell carcinoma (MRCC) is one of the malignancies that are sensitive to immunotherapy. However, the underlying immune inhibitory factors such as myeloid-derived suppressor cells (MDSCs) might restrain the efficacy of immunotherapy. The present study investigates the clinical efficacy of cytokine-induced killer (CIK) cell therapy in patients with MRCC and explores whether the levels of peripheral MDSCs are associated with the prognosis of patients receiving this therapy. Twenty-nine patients with measurable MRCC were treated with an adoptive transfer of autologous CIK cells, followed by 5 consecutive days of interleukin-2 administration. The tumor response and 1-year survival were observed. The proportion of MDSCs in the peripheral blood was detected, and the correlation of MDSCs with prognosis was analyzed. Of 29 evaluable patients, no complete responses were seen; 4 patients exhibited a partial response (13.8%), 18 patients displayed stable disease (62.1%), and 7 patients showed progressive disease (24.1%). Twenty patients (69.0%) were alive 14.8–41.4 months at the time of the last follow-up (median follow-up=20.2 mo). The 1-year survival was 82.8% (24/29). Peripheral blood MDSCs were elevated in almost all MRCC patients and decreased after CIK-cell infusion. Subgroup analysis indicated that patients with a relatively low proportion of MDSCs exhibited prolonged survival. In conclusion, our data suggest that transfusion of autologous CIK cells can induce regression of MRCC, and MDSCs can serve as a potential marker for the prognosis of patients receiving a CIK-based therapy.

Efficacy of RetroNectin-Activated Cytokine-Induced Killer Cell Therapy in Metastatic Brain Tumor Patients

Background: The aim of this study was to investigate the clinical efficacy of RetroNectin-activated cytokine-induced killer cell (R-CIK) therapy following conventional therapies in patients with metastatic brain tumors. Methods: This study included 20 patients with metastatic brain tumors. Patients received R-CIK therapy following conventional therapies (including chemotherapy and target therapy). Progression-free survival (PFS), overall survival (OS), and prognostic factors were evaluated. Results: Of the 4 breast cancer patients in our cohort, 2 remained alive and 2 died. Of the 14 non-small cell lung cancer (all adenocarcinoma) patients, 3 had a partial response, 8 had stable disease, and 3 had progressive disease after receiving R-CIKs. The overall response rate was 21.4% (3/14), and the disease control rate was 78.6% (11/14). The median PFS and OS were 7.7 months (95% confidence interval (CI) 3-16.5 months) and 12.6 months (95% CI 6-21 months), respectively. Conclusion: R-CIKs combined with conventional therapies could improve the prognosis of metastatic brain tumor patients, especially of those with adenocarcinoma of the lung.

Angiogenesis inhibitors rechallenge in patients with advanced non-small-cell lung cancer: a pooled analysis of randomized controlled trials.

Purpose Data on the role of angiogenesis inhibitors (AIs) rechallenge in the treatment of advanced non-small-cell lung cancer (NSCLC) patients who previously received bevacizumab remain limited. We aim to investigate the efficacy of AIs in the treatment of advanced NSCLC in this setting. Methods Studies from PubMed, Web of Science, and abstracts presented at American Society of Clinical Oncology meeting up to December 1, 2014 were searched to identify relevant studies. Eligible studies included prospective randomized controlled trials evaluating AIs in advanced NSCLC, with survival data on patients who previously received bevacizumab. The end points were overall survival and progression-free survival. Statistical analyses were conducted by using either random effects or fixed effect models according to the heterogeneity of included studies. Results A total of 452 patients with advanced NSCLC who previously received bevacizumab were identified for analysis. The meta-analysis results demonstrated that AI rechallenge significantly improved progression-free survival (hazard ratio: 0.72, 95% confidence interval: 0.58–0.89, P=0.002) when compared to non-AI containing regimens. Additionally, a nonsignificant improvement in overall survival was also observed in advanced NSCLC in this setting (hazard ratio: 0.82, 95% confidence interval: 0.65–1.03, P=0.087). Similar results were also observed in subgroup analysis according to treatment regimens. Conclusion The findings of this study suggest that NSCLC patients who relapsed after a first-line bevacizumab-containing chemotherapy obtain improved clinical benefits from AI rechallenge. Prospective clinical trials investigating the role of AI rechallenge in this setting are recommended.

Survival benefit from RectroNectin-activated cytokine-induced killer cells combined with chemotherapy in advanced EGFR wild-type lung adenocarcinoma

AIM To investigate the efficacy of chemotherapy and RectroNectin-activated cytokine-induced killer (R-CIK) cell immunotherapy in patients with advanced EGFR wild-type lung adenocarcinoma. METHODS Using data gathered from a single institution, 125 patients with stage IIIB or IV EGFR wild-type lung adenocarcinoma between January 2009 and June 2015 were identified and enrolled in this retrospective study. RESULTS The disease control rates and median overall survival was better in R-CIK group compared with control group. Multivariate survival analysis showed that R-CIK cell treatment was an independent prognostic factor for overall survival. CONCLUSION R-CIK cell immunotherapy may prolong survival of patients with advanced EGFR wild-type lung adenocarcinoma.

Angiotensin-(1-7)-mediated Mas1 receptor/NF-κB-p65 signaling is involved in a cigarette smoke-induced chronic obstructive pulmonary disease mouse model

Angiotensin‐(1‐7) [Ang‐(1‐7)] has been shown to play a significant role in the pathogenesis of lung inflammation via Mas receptor; however, its effect in chronic obstructive pulmonary disease (COPD) remains unknown. To explore the effect of Ang‐(1‐7) on a cigarette smoke (CS) exposure‐induced COPD model, 40 C57BL/6J mice were divided into four groups (n = 10) and exposed to air or CS for 8 weeks. After that, they were treated with saline or Ang‐(1‐7) at 0.3 mg/kg for 2 weeks by subcutaneous infusion using osmotic pump. The day following drug/vehicle challenge, lung function was examined and bronchoalveolar lavage (BAL) was performed. Chemokine (C–X–C motif) ligand 1, interleukin‐6, and tumor necrosis factor‐α protein levels in BAL fluid were determined using ELISA; the corresponding mRNA levels in lung tissues were measured using RT‐PCR. Mas1 receptor, pIκBα, IκBα, nuclear NF‐κB‐p65 protein, pERK1/2, ERK2, pp38, and p38 proteins expression in lung tissues were examined by immunohistochemical staining and western blotting. Ang‐(1‐7) challenge had no effect on the decreased lung function and emphysema induced by CS exposure. However, Ang‐(1‐7) treatment blocked CS exposure‐induced lung inflammatory responses and lung fibrosis, as determined by Massons Trichrome staining. Exposure to CS for 8 weeks caused irreversible loss of lung function and emphysema, which could not be reversed by Ang‐(1‐7) treatment. Thus, the beneficial effect of Ang‐(1‐7) may be confined to pulmonary inflammation and fibrosis.

Treatment of relapsed/refractory (R/R) B-cell malignancies by chimeric antigen receptor T cells cultured from 50-100 mL peripheral blood in 7-10 days.

7034Background: Anti-CD19 chimeric antigen receptor (CAR) T cells for R/R B-cell malignancies has been remarkably effective in recent clinical trials. However, the training process is complex and l...

Rapid complete remission of metastatic melanoma after first-line treatment with nivolumab plus tumor-infiltrating lymphocytes

Melanoma is the most common type of skin cancer in both men and women in the USA. The standard treatment modality for advanced melanoma is immunotherapy, either alone or in combination. As single-agent immunotherapy is usually inadequate, combined immunotherapy might be a good choice and combined treatment modalities appropriate for melanoma need to be explored. Herein, we report a case of metastatic melanoma successfully treated with combined therapy of tumor-infiltrating lymphocytes and nivolumab. Complete remission was achieved approximately 4 months after the initiation of treatment. The treatment was well tolerated and only grade 1 fatigue occurred. The patient was still on complete remission 1 year after stopping the treatment. Our result showed that this treatment modality might be an ideal option for patients with metastatic melanoma.

Nivolumab-induced cytokine-release syndrome in relapsed/refractory Hodgkin's lymphoma: a case report and literature review

Hodgkins lymphoma is a common malignant disease, especially among children in America. Although chemotherapy and radiotherapy are mainstay treatments for Hodgkins lymphoma, a small portion of patient experiences relapsed or refractory diseases. Nivolumab provides an option for patients who experience relapsed or refractory disease, but adverse effects may occur. Here, we report a patient with relapsed/refractory Hodgkins lymphoma who experienced cytokine-release syndrome after his first dose of nivolumab. The patient eventually experienced complete remission after his fifth dose of nivolumab. Cytokine-release syndrome might reflect good efficacy during treatment of relapsed/refractory Hodgkins lymphoma with nivolumab. However, health care providers, should stay alert and take appropriate measures if adverse effects, such as cytokine-release syndrome, occur.

Combination of PD-1 blockade and RetroNectin-activated cytokine-induced killer in preheavily treated non-small-cell lung cancer: a retrospective study

AIM To analyze the efficacy of PD-1 blockade combined with RetroNectin®-activated cytokine-induced killer (R-CIK) cells in preheavily treated advanced non-small-cell lung cancer (NSCLC). METHODS We retrospectively analyzed patients with advanced NSCLC who received PD-1 blockade combined with R-CIK cells whose treatments failed at least two regimens. RESULTS The median number of previous treatment regimens was three (range: 2-7). Partial remission was achieved in two patients, stable disease in four patients and one patient experienced progressive disease. The median time-to-progression was 4.8 months. CONCLUSION PD-1 blockade combined with R-CIK cells is safe and effective in patients with advanced NSCLC who have failed at least two treatment regimens.

T‑cell immunoglobulin and mucin domain‑containing protein‑3 and galectin‑9 protein expression: Potential prognostic significance in esophageal squamous cell carcinoma for Chinese patients

The aim of the present study was to investigate the expression levels of the T-cell immunoglobulin and mucin domain-containing protein-3 (TIM-3) and galectin-9 proteins and their clinical value in esophageal squamous cell carcinoma (ESCC) in Chinese patients. The expression profiles of TIM-3 and galectin-9 in ESCC were determined by the immunohistochemical analysis of the postoperative pathological specimens of 45 patients with ESCC; a χ2 test was used to evaluate the association of TIM-3 and galectin-9 expression with clinicopathological parameters, in addition to univariate and multivariate Coxs proportional hazards model to analyze the prognostic value of the expression of TIM-3 and galectin-9 proteins. The proportion of samples exhibiting a high staining intensity for TIM-3 and galectin-9 were 22.22 and 15.56%, respectively: these samples were termed the TIM-3 high-expression group (HEG) and galectin-9-HEG. There was a negative correlation between the expression of TIM-3 and galectin-9 (R=−0.71, P<0.001). The results of Kaplan-Meier survival analysis led to the conclusion that, compared with the TIM-3 low expression group (LEG), patients in the TIM-3-HEG exhibited a poorer overall survival rate (χ2=6.049, P=0.0139). By contrast, patients in the galectin-9-HEG exhibited a significantly better overall survival rate than those in the galectin-9-LEG (χ2=4.915, P=0.0266). However, the levels of TIM-3 and galectin-9 expression were not identified as independent indicators for the prognosis of patients with ESCC. As high TIM-3 and low galectin-9 expression levels were associated with a poor prognosis for patients with ESCC in the present study, these proteins may be potential prognostic indicators for ESCC.