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:

Serial assessment of circulating T lymphocyte phenotype and receptor repertoire during treatment of non-muscle invasive bladder cancer with adoptive T cell immunotherapy.

Recurrence and progression of non-muscle-invasive bladder cancer (NMIBC), frequent despite the availability of multiple treatment modalities, may be partly explained by the presence of immunosuppressive cell populations. We hypothesized that progression of disease could be prevented by the administration of an activated T cell immunotherapy (ACT) at time points when immunosuppressive populations increased in peripheral blood. In an N-of-1 study, a patient with multiple primary bladder high grade urothelial carcinomas, previously treated with standard local resection and chemotherapy but with evidence of progression, received ACT consisting of dendritic cells mixed with cytokine induced killer cells (DC/CIK), intravenously 18 times over a 6 year period at indicated time of observed increases in peripheral blood immunosuppressive CD8+/CD28- cells. Peripheral blood was analyzed for T cell phenotype by flow cytometry, T cell receptor (TCR) repertoire, and circulating tumor DNA (ctDNA) by next generation sequencing (NGS) at the time of each infusion. Cystoscopy and pelvic CT scans were performed at routine intervals to assess clinical status of disease. There has been no recurrence or metastasis of urothelial carcinoma. Peripheral blood cytotoxic T cells and unique TCR clones increased and suppressive T cell populations decreased after DC/CIK infusions evidenced by the two more proof-of concept cases. ctDNA analysis detected mutations in six genes (ARID1B, MYCN, CDH23, SETD2, NOTCH4 and FAT1) which appeared at different times, but all of them disappeared after the DC-CIK infusions. These data suggest that DC/CIK infusions may be associated with beneficial changes in T cell phenotype, TCR repertoire, decreases in circulating tumor DNA and sustained recurrence-free survival.
Authors
Wang, X; Qiao, G; Jiang, N; Morse, MA; Zhou, X; Wang, S; Wu, J; Song, Y; Zhao, Y; Zhou, L; Yuan, Y; Hobeika, A; Ren, J; Lyerly, HK
URI
https://scholars.duke.edu/individual/pub1481912
PMID
33948384
Source
pubmed
Published In
American Journal of Cancer Research
Volume
11
Published Date
Start Page
1709
End Page
1718

Blood microbiota diversity determines response of advanced colorectal cancer to chemotherapy combined with adoptive T cell immunotherapy.

Human microbiota influence the response of malignancies to treatment with immune checkpoint blockade; however, their impact on other forms of immunotherapy is poorly understood. This study explored the effect of blood microbiota on clinical efficacy, represented by progression-free survival (PFS) and overall survival (OS), of combined chemotherapy and adoptive cellular therapy (ACT) in advanced colon cancer patients. Plasma was collected from colorectal cancer patients (CRC) treated with either chemotherapy alone (oxaliplatin and capecitabine) (XELOX CT alone group, n = 19), or ACT with a mixed dendritic cell/cytokine-induced killer cell product (DC-CIK) + XELOX (ICT group, n = 20). Circulating microbiota analysis was performed by PCR amplification and next-generation sequencing of variable regions V3~V4 of bacterial 16S rRNA genes. The association of the blood microbial diversity with clinical response to the therapy as measured by RECIST1.1 and OS was evaluated. The baseline Chao index of blood microbial diversity predicted prolonged PFS and OS of DC/CIK immunotherapy. More diverse blood microbiota that included Bifidobacterium, Lactobacillus, and Enterococcus were identified among responders to DC/CIK compared with non-responders. The plasma bacterial DNA copy number is inversely correlated with the CD3-/CD16+/CD56+ NK cells in circulation and decreased following DC-CIK; however, the Chao index of plasma microbiota significantly increased after administration of the DC-CIK product and this subsequent change was correlated with the number of CD3-/CD16+/CD56+ and CD8+/CD28+ cells infused. The diversity of the blood microbiome is a promising predictive marker for clinical responses to chemotherapy combined with DC-CIK. Cellular immunotherapy can affect the plasma microbiota's diversity in a manner favorable to clinical responses.
Authors
Yang, D; Wang, X; Zhou, X; Zhao, J; Yang, H; Wang, S; Morse, MA; Wu, J; Yuan, Y; Li, S; Hobeika, A; Lyerly, HK; Ren, J
MLA Citation
Yang, Duo, et al. “Blood microbiota diversity determines response of advanced colorectal cancer to chemotherapy combined with adoptive T cell immunotherapy.Oncoimmunology, vol. 10, no. 1, 2021, p. 1976953. Pubmed, doi:10.1080/2162402X.2021.1976953.
URI
https://scholars.duke.edu/individual/pub1498110
PMID
34595059
Source
pubmed
Published In
Oncoimmunology
Volume
10
Published Date
Start Page
1976953
DOI
10.1080/2162402X.2021.1976953

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: Radiation therapy (RT) modulates immune cells and cytokines, resulting in both clinically beneficial and detrimental effects. The changes in peripheral blood T lymphocyte subsets and cytokines during RT 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, aged 3~18) with primary brain tumors (medulloblastoma, glioma, germ cell tumors (GCT), and central nervous system embryonal tumor-not otherwise specified), with or without residual or disseminated (R/D) diseases who were starting standard postoperative focal or craniospinal irradiation (CSI). Peripheral blood T lymphocyte subsets collected before and 4 weeks after RT were enumerated by flow cytometry. Plasma levels of interleukin (IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor-α, interferon-γ, and IL-17A were measured by cytometric bead array. RESULTS: Patients with R/D lesions receiving CSI (n = 32) had a post-RT increase in the frequency of CD3+T and CD8+T cells, a decrease in CD4+T cells, and an increase in regulatory T cells (Tregs) and CD8+CD28- suppressor cells, which was more predominantly seen in these patients than in other groups. In the CSI group with such R/D lesions, 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 after RT. The post/pre-RT ratio of Tregs (P = .0493), IL-6 (P = .0111), and IL-10 (P = .0070) was lower in the CR group than in the PR group. Multivariate analysis revealed that the post/pre-RT ratios of Treg, IL-6, and IL-10 were independent predictors of CR (P < .0001, P = .018, P < .0001, respectively). The areas under the receiver operating curves and confidence intervals were 0.7652 (0.5831-0.8964), 0.7794 (0.5980-0.9067), and 0.7085 (0.5223-0.8552) 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 predominantly exerted an effect on antitumor immune response compared with both R/D lesion-free but exposed to focal or CSI RT and with R/D lesions and exposed to focal RT. 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 to 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
MLA Citation
Song, Linan, et al. “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.Int J Radiat Oncol Biol Phys, vol. 111, no. 2, Oct. 2021, pp. 479–90. Pubmed, doi:10.1016/j.ijrobp.2021.04.041.
URI
https://scholars.duke.edu/individual/pub1481989
PMID
33974888
Source
pubmed
Published In
Int J Radiat Oncol Biol Phys
Volume
111
Published Date
Start Page
479
End Page
490
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