Jun Ren

Overview:

Jun Ren MD, PhD  joined Duke University as faculty from 2008. He has actively worked with Professor Kim Lyerly to create the global cancer programs featured on education and research on  cancer immunotherapy and cancer vaccinewith Capital University Cancer Center,Beijing, China. They have been keeping pursuing to set up the win-to-win platform thought overcoming these differences and difficulties between US and China since 2008. He and Kim Lyerly secured the transitional research for cancer immunotherapy and achieved clinical research success and expand the global academic prospectives  of Duke University.

Positions:

Visiting Scholar in the Comprehensive Cancer Center

Duke Cancer Institute
School of Medicine

Publications:

Changes in peripheral blood regulatory T cells, and IL-6 and IL-10 levels predict response of pediatric medulloblastoma and germ cell tumors with residual or disseminated disease to craniospinal irradiation.

PURPOSE: Radiotherapy modulates immune cells and cytokines resulting in both clinically beneficial and detrimental effects. The changes in peripheral blood T lymphocyte subsets and cytokines during radiotherapy for pediatric brain tumors and the association of these changes with therapeutic outcomes have not been well described. METHODS AND MATERIALS: The study population consisted of children (n=83, ages 3∼18) with primary brain tumors (medulloblastoma, glioma, germ cell tumors, and CNS embryonal tumor-NOS), with or without residual or disseminated (R/D) diseases who were starting standard post-operative focal or craniospinal-irradiation (CSI). Peripheral blood T lymphocyte subsets collected before and 4 weeks after radiotherapy were enumerated by flow cytometry. Plasma levels of IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ, and IL-17A were measured by cytometric bead array. RESULTS: Patients with R/D lesions receiving CSI (n=32) had a post-radiotherapy increase in the frequency of CD3+T cell and CD8+T cells, a decrease in CD4+ T cells, and an increase in Tregs and CD8+CD28- suppressor cells which were predominantly seen than other groups. In such R/D lesions exposed to CSI group, consisting of patients with medulloblastoma and germ cell tumors, 19 experienced a complete response (CR) and 13 experienced a partial response (PR) on imaging at 4 weeks following radiotherapy. The post/pre-radiotherapy ratio of Tregs (P =0.0493), IL-6 (P=0.0111) and IL-10 (P=0.0070) was lower in the CR group than the PR group. Multivariate analysis revealed that the post/pre-radiotherapy ratios of Treg, IL-6 and IL-10 were independent predictors of CR (P<0.0001, P=0.018, P<0.0001, respectively). The areas under the receiver operating curves (ROC) and confidence intervals were 0.7652 (0.5831ཞ0.8964), 0.7794 (0.5980ཞ0.9067), 0.7085 (0.5223ཞ0.8552) for IL-6, IL-10 and Treg respectively. The sensitivities of IL-6, IL-10 and Treg to predict radiotherapeutic responses were 100%, 92.3%, and 61.5% and specificity was 52.6%, 57.9%, and 84.2% respectively. CONCLUSIONS: CSI treatment to those with R/D lesions exerted a predominantly effect on anti-tumor immune response compared with both R/D lesions-free but exposed to focal or CSI radiotherapy and with R/D lesions for focal radiotherapy. Such CSI with R/D lesions group experiencing CR is more likely to have a decrease in immunoinhibitory molecules and cells than patients who only achieve PR. Measuring peripheral blood Treg, IL-6 and IL-10 levels could be valuable for predicting radiotherapeutic responses of pediatric brain tumors with R/D lesions with CSI for medulloblastoma and intracranial germ cell tumors.
Authors
Song, L; Wang, S; Fang, T; Qiu, X; Wang, X; Zhou, X; Morse, MA; Hobeika, A; Wu, W; Yang, H; Ren, J; Lyerly, HK
URI
https://scholars.duke.edu/individual/pub1481989
PMID
33974888
Source
pubmed
Published In
Int J Radiat Oncol Biol Phys
Published Date
DOI
10.1016/j.ijrobp.2021.04.041

Clinical efficacy of intra-cavitary infusions of autologous dendritic cell/cytokine-induced killer cell products for the treatment of refractory malignant pleural effusions and ascites.

To explore the safety and efficacy of intra-cavitary infusions of autologous mixed dendritic cell (DC)-cytokine-induced killer (CIK) cell products in advanced cancer patients with malignant pleural effusions or ascites. DC-CIKs were expanded ex vivo (mean yield of 1.36×109 cells (range, 0.74~4.98×109)) from peripheral blood mononuclear cells obtained by repeated venipuncture or apheresis. Patients received at least 1 cycle of 3 infusions of the DC-CIKs administered by indwelling catheter into the pleural or peritoneal cavity every other day. The volume of malignant effusions was assessed radiologically. Peripheral blood lymphocyte populations were enumerated by flow cytometry. Quality of life (QoL) during the DC-CIK infusions was assessed by the EORTC QLQ-30 instrument. ctDNA sequencing was performed to analyze gene clonal load and molecular tumor burden during the infusion treatment. Thirty-seven patients with breast, lung and other malignancies were enrolled. The results showed that intra-cavitary DC-CIK infusions (16 intrapleural and 21 intraperitoneal) were well-tolerated with no grade 3/4 adverse events. There was one complete response with effusion disappearance (CR) (3%), 13 partial responses (PR) (35%), 12 with stable disease (SD) (32%) and 11 with progressive disease (PD) (30%), resulting in a clinical effusion control rate (CCR) of 70% (26/37). The total number of infused CIKs and the CD3+/CD8+ and CD8+/CD28+ T cell frequencies within the CIKs were associated with effusion control (P=0.013). Moreover, increased peripheral blood CD3+/CD8+ (P=0.035) and decreased CD4+/CD25+ T cell frequencies (P=0.041) following the DC-CIK infusions were associated with malignant effusion and ascites control. Reductions in ctDNA correlated with clinical benefit. In conclusion, intra-cavitary autologous cellular immunotherapy is an alternative method to effectively control malignant pleural effusions and ascites. The overall effusion control rate was associated with higher peripheral blood effector T cell frequencies.
Authors
He, Z; Wang, S; Qiao, G; Wang, X; Zhou, X; Zhu, S; Yuan, Y; Morse, MA; Hobeika, A; Ren, J; Lyerly, HK
URI
https://scholars.duke.edu/individual/pub1454060
PMID
32774747
Source
pubmed
Published In
American Journal of Translational Research
Volume
12
Published Date
Start Page
3940
End Page
3952

Infiltration of metastatic lymph nodes with PD-1+ T cells is associated with improved disease-free and overall survival in resected N+ NSCLC.

Tumor metastases to regional lymph nodes are associated with worse outcome for patients with resected non-small cell lung cancer (NSCLC), but there is a wide variation in survival. We hypothesized that infiltration of tumor-involved lymph nodes with activated effector T cells would impact subsequent outcome. A total of 54 lymph nodes (27 N+ and 15 N- collected from 12 patients with Stage IIB (T2N1M0) and 12 N- lymph nodes collected from 10 patients with Stage IIA (T2N0M0) who underwent lymphadenectomy during surgical management of their NSCLC) were analyzed for effector T cells expressing activation markers PD-1 and TIM-3 using the Opal-multiple immunofluorescence assay. The frequency of CD3+CD8+ (P=0.0001), CD3+CD8+TIM-3+ (P<0.0001), and CD3+CD8+TIM-3+Ki-67+ (P<0.0001) T cells was greater in lymph nodes of IIA patients compared with IIB patients; however the frequency of CD3+CD8+PD-1+ (P=0.0086), CD3+CD8+TIM-3+ (P=0.0129), CD3+CD8+PD-1+Ki-67+ (P<0.0001) and CD3+CD8+TIM-3+Ki-67+ (P=0.0001) T cells was greater among the tumor involved (N+) nodes of N1 patients compared with the tumor-uninvolved (N-) nodes. The frequency of intranodal CD3+CD8+, CD3+CD8+PD-1+ and CD3+CD8+PD-1+Ki-67+ T cells in N+ nodes was associated with prolonged progression-free (PFS) and overall survival (OS). These data suggest that CD3+CD8+TIM-3+ T cells may suppress tumor spread to regional lymph nodes but once tumor cells metastasize to lymph nodes, CD3+/CD8+/PD-1+/Ki67+ T cells localizing to N+ nodes may prevent further tumor spread, resulting in prolonged survival.
Authors
Wang, S; Song, Y; Morse, MA; Sun, P; Qiao, G; Wang, X; Zhou, X; Hobeika, A; Ren, J; Lyerly, HK
MLA Citation
URI
https://scholars.duke.edu/individual/pub1470730
PMID
33415009
Source
pubmed
Published In
American Journal of Cancer Research
Volume
10
Published Date
Start Page
4435
End Page
4449

DC-CIK as a widely applicable cancer immunotherapy.

Introduction: Immunotherapy is now a standard treatment for many malignancies. Although immune checkpoint inhibition has demonstrated substantial efficacy by enhancing T cell activation and function in the tumor microenvironment, adoptive transfer of T and NK cell products promises to provide activated cells capable of immediate and direct tumor destruction. A widely applicable, non-MHC dependent, cellular therapy, consisting of in vitro generated dendritic cells (DC) combined with cytokine-induced killer cells (CIK), is highly efficient to produce from individual patients and has demonstrated safety and efficacy alone or with chemotherapy.Areas covered: We summarize the clinical data from studies of DC-CIK and discuss future research directions.Expert opinion: Patients with a wide variety of tumor types who have received DC-CIK therapy may experience clinical responses. This versatile therapy synergizes with other anti-cancer therapies including chemotherapy and immunotherapy.
Authors
MLA Citation
Wang, Shuo, et al. “DC-CIK as a widely applicable cancer immunotherapy.Expert Opin Biol Ther, vol. 20, no. 6, June 2020, pp. 601–07. Pubmed, doi:10.1080/14712598.2020.1728250.
URI
https://scholars.duke.edu/individual/pub1431187
PMID
32033522
Source
pubmed
Published In
Expert Opin Biol Ther
Volume
20
Published Date
Start Page
601
End Page
607
DOI
10.1080/14712598.2020.1728250

Predictive significance of T cell subset changes during ex vivo generation of adoptive cellular therapy products for the treatment of advanced non-small cell lung cancer.

Adoptive T cell immunotherapy with cytokine-induced killer cells (CIKs) has been demonstrated to prolong the survival of patients with advanced non-small cell lung cancer (NSCLC). The aim of the present study was to evaluate whether the expansion of effector T cells and the decrease of regulatory T cells (Tregs) that occurred during the ex vivo generation of DC-CIKs were associated with improved clinical outcome in patients who received treatment. CIKs were generated ex vivo over a 28-day period from the peripheral blood apheresis product of 163 patients with advanced cancer (including 30 with NSCLC). CIKs were also generated from an additional cohort of 65 patients with NSCLC over a 15-day period. The progression-free survival (PFS) and overall survival (OS) time of patients treated with CIKs was determined by reviewing the patients' medical records. The number of CIKs gradually increased during the culture period and peaked at day 15, followed by a slight decline until day 28. Similarly, the percentages of T cell subtypes associated with anti-tumor activity (CD3+, CD3+CD4+, CD3+CD8+ and CD8+CD28+) peaked at day 15. Although the percentage of CD4+CD25+CD127+ Tregs increased by day 7, a decrease was subsequently observed. Among the 95 patients with NSCLC, those with a post/pre-culture ratio of CD8+CD28+ T lymphocytes >2.2 had significantly better PFS and OS compared with those with ratios ≤2.2. Those with a post/pre-culture CD4+CD25+CD127+ Treg ratio ≤0.6 had significantly better OS and PFS compared with those with ratios >0.6. The peak expansion of CIKs from peripheral blood mononuclear cells occurred at day 15 of ex vivo culture. PFS and OS were associated with post/pre-culture CD8+CD28+ T lymphocyte ratio >2.2 and post/pre-culture CD4+CD25+CD127+ Treg ratio <0.6 in the CIKs of patients with advanced NSCLC treated with adoptive T cell immunotherapy. Further efforts are underway to optimize the DC-CIK infusion for cancer immunotherapy.
Authors
Huang, L; Qiao, G; Morse, MA; Wang, X; Zhou, X; Wu, J; Hobeika, A; Ren, J; Lyerly, HK
MLA Citation
Huang, Lefu, et al. “Predictive significance of T cell subset changes during ex vivo generation of adoptive cellular therapy products for the treatment of advanced non-small cell lung cancer.Oncol Lett, vol. 18, no. 6, Dec. 2019, pp. 5717–24. Pubmed, doi:10.3892/ol.2019.10964.
URI
https://scholars.duke.edu/individual/pub1423209
PMID
31788044
Source
pubmed
Published In
Oncology Letters
Volume
18
Published Date
Start Page
5717
End Page
5724
DOI
10.3892/ol.2019.10964