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ORIGINAL ARTICLE
Year : 2018  |  Volume : 14  |  Issue : 9  |  Page : 427-432

Retrospective analysis on the efficacy of sunitinib/sorafenib in combination with dendritic cells-cytokine-induced killer in metastasis renal cell carcinoma after radical nephrectomy


1 Department of Urology, Affiliated Hospital of Academy of Military Medical Sciences, Beijing 100071, China
2 Department of Urology, Clinical College, No. 307 Hospital of PLA, Anhui Medical University, Beijing 100071, China
3 Department of Hematopoietic Stem Cell Transplantation, Affiliated Hospital of Academy of Military Medical Sciences; Cell and Gene Therapy, Academy of Military Medical Sciences, Beijing 100071, China
4 Department of Medical Molecular Biology, Beijing Institute of Biotechnology, 27 Tai-Ping Lu Rd, Beijing 100850, China
5 Department of Urology, Affiliated Hospital of Academy of Military Medical Sciences; Department of Urology, Clinical College, No. 307 Hospital of PLA, Anhui Medical University, Beijing 100071, China

Date of Web Publication29-Jun-2018

Correspondence Address:
Li-Jun Chen
Department of Urology, Affiliated Hospital of Academy of Military Medical Sciences, Beijing 100071
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.180609

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 > Abstract 

Objective: Sunitinib/sorafenib (SU/SO), dendritic cells (DCs), or DC-cytokine-induced killer (CIK) could significantly prolong progression-free survival (PFS), 3-year overall survival (OS), or 5-year OS for patients with metastatic renal cell carcinoma (mRCC). We retrospectively analyzed the clinical efficacy between SU/SO combined with DC-CIK and SU/SO monotherapy in treating renal cell carcinoma (RCC) patients with metastasis after radical nephrectomy.
Materials and Methods: All patients (n = 34) with postoperative mRCC in our hospital from January 2009 to January 2014 were received either SU/SO monotherapy (Group 1, n = 15) or in combination with DC-CIK (Group 2, n = 19). A retrospective study was based on the primary endpoint (PFS) and secondary endpoint (OS).
Results: At a median follow-up of 19.5 months, in Group 2, as compared with in Group 1, the median PFS was significantly longer (28.0 vs. 11.0 months, P = 0.03). Moreover, the 3-year OS was higher (57.1% vs. 28.6%). The cases of progressive diseases (PDs) and deaths were less in Group 2 than that in Group 1 (PD: 8 vs. 9, deaths: 3 vs. 5); however, the cases of stable diseases were more (11 vs. 6). In addition, the 3-year OS was higher in SU + DC-CIK group than that in SO + DC-CIK group (63.36% vs. 50%). There was no significant difference for PFS between SO + DC-CIK group and SU single agent group.
Conclusions: SU/SO with DC-CIK could significantly prolong the median PFS, improve the 3-year OS rate, prolong the 3-year OS. It is likely to be a new approach for mRCC after radical nephrectomy.

Keywords: 3-year overall survival, dendritic cells-cytokine-induced killer, metastatic renal cell carcinoma, progression-free survival, radical nephrectomy, sorafenib, sunitinib


How to cite this article:
Mai HX, Mei GH, Zhao FL, Li BT, Tang YY, Zhang B, Xu XJ, Chen LJ. Retrospective analysis on the efficacy of sunitinib/sorafenib in combination with dendritic cells-cytokine-induced killer in metastasis renal cell carcinoma after radical nephrectomy. J Can Res Ther 2018;14, Suppl S2:427-32

How to cite this URL:
Mai HX, Mei GH, Zhao FL, Li BT, Tang YY, Zhang B, Xu XJ, Chen LJ. Retrospective analysis on the efficacy of sunitinib/sorafenib in combination with dendritic cells-cytokine-induced killer in metastasis renal cell carcinoma after radical nephrectomy. J Can Res Ther [serial online] 2018 [cited 2019 Jul 19];14:427-32. Available from: http://www.cancerjournal.net/text.asp?2018/14/9/427/180609


 > Introduction Top


The common malignant tumor in the adult urinary system, renal cell carcinoma (RCC), is treated mainly by radical nephrectomy because of its sensitivity to neither chemotherapy nor radiotherapy. Moreover, 25% of them recur earlier in diagnosis. And 9% of patients with localized RCC will recur after radical nephrectomy in 5 years.[1] Patients with metastatic RCC (mRCC) had a poor prognosis, and the median survival was 6–12 months.[2],[3] Targeted therapy or immunotherapy could significantly prolong the progression-free survival (PFS) and survival of patients with mRCC after radical nephrectomy.[4],[5] However, targeted therapy drugs lead to adverse events (AEs), such as fatigue, hypertension, hand-foot syndrome, and bone marrow suppression; it will decrease the quality of life.

Dendritic cells (DCs), the most power antigen presenting cells (APC), could regulate the immune response of body by stimulating activation and proliferation of T lymphocyte. The efficiency of autologous DC vaccine has been observed in treating mRCC.[6] Despite the easily occurred refractoriness from tumor cells by monotherapy, the combination regimens, might decrease refractoriness. However, the key question was how to combine. SU will not change the function and phenotype of DC, and it was suitable for combination with DC in treating RCC.[7] Moreover, the addition of cytokine-induced killer (CIK) into SU treated-DC showed an enhanced antitumor response.[8] The results of previous research demonstrate the availability of joint therapy of SU and DC-CIK in treating mRCC, and the clinical efficacy was obvious. However, sunitinib/sorafenib (SU/SO) in combination with DC-CIK in treating mRCC has not been reported. We hope the results can provide a reference for other researchers, and the combination regimens probably to be a new therapeutic option.

Our study summarized data from our division of patients receiving either SU or another agent, SO, in combination with DC-CIK in treating postoperative mRCC, and investigated PFS, overall survival (OS), progressive disease (PD), stable disease (SD), AE, and mortality. The results indicated the apparently longer PFS and OS, and lower AE rate in combination therapy.


 > Materials and Methods Top


Patients

From January 2009 to January 2014, all 34 patients with postoperative mRCC (25 males and nine females with age 58.40 ± 9.07 vs. 53.21 ± 10.28) in our hospital were received either SU/SO (n = 15) or in combination with DC-CIK (n = 19). The patients were diagnosed by pathology and clinical stage of the all cases was III~IV (AJCC Kidney Cancer Staging Standard 2009). There were no significant differences of the gender, age, and clinical stage. The tumor pathological types are shown in [Table 1]. This study was conducted in accordance with the Declaration of Helsinki. This study was conducted with approval from the Ethics Committee. Written informed consent was obtained from all participants.
Table 1: Pathological type of patients in Group 1 and 2

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Generation of dendritic cells and cytokine-induced killer cells

The DC vaccine and CIK cells were obtained as previously described.[9],[10],[11] And DC vaccine was stimulated by autologous tumor cell antigen. In summary, DC and CIK were generated from peripheral blood mononuclear cells (PBMC) from patients themselves. PBMC were adhered in a petri dish (100 mm) at a density of 1 × 108 cells/ml for 30 min at 37°C in X-vivo medium (Lonza). 400 U/ml recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF, PeproTech) and 500 U/ml recombinant human IL-4 (rhIL-4, PeproTech) were added for 5 days. Mature DC (mDC) was achieved by adding 100 U/ml tumor necrosis factor α (TNF-α, PeproTech) on day 6 for 24 h. Nonadherent PBMC was suspended in X-vivo medium containing 50 ηg/mL anti-CD3 antibody to generate CIK cells. 1000 U/ml human interferon-γ (IFN-γ) (PeproTech) was added and incubated at 37°C, 5% CO2 for 24 h. After incubation, 300 IU/ml rhIL-2 (rhIL-2, PeproTech) was added to the media. The cells were maintained at a density of 5 × 109 cells/ml in X-vivo medium, with medium replacement every 5 days. CIK cells were harvested on day 13.

Treatments

All patients provided written consent before administering the two treatments. The patients were treated with SU/SO in Group 1 (n = 15) and treated with SU/SO in combination with DC-CIK (n = 19). 50 mg SU (Pfizer, America) was started daily after 2-3 weeks of radical nephrectomy, the daily dose administered 4 weeks on/2 weeks off schedule. The patients were treated with 600 mg SO (Bayer, Germany) twice daily with 14-day interval every 4 weeks. If the patient suffered from Grade III–IV of AEs, he/she will be stopped or reduced dose to SU 25 mg/day or SO 400 mg/time. Then, DC was injected subcutaneously about 1–5 × 107/ml on day 7, 9, 11, and 13, the CIK was injected intravenously about 5–10 × 109/ml on day 13.

Adverse events

AE among those hospitalized patients was evaluated by their vital signs, status, routine blood, liver function, kidney function and thyroid function, etc.; AEs among those nonhospitalized patients were evaluated by questionnaire.

Stratified by National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0 (CTCAE) (Publish Date: August 9, 2006) PFS were calculated based on dates of chest X-ray, chest/abdomen computerized tomography (CT), and positron emission tomography-CT.

Statistical analysis

Either grouped t-tests or nonparametric tests were performed based on normality while comparing two groups. Survival analyses were performed with Kaplan–Meier method. All statistics analyses were performed with SPSS 16.0.


 > Results Top


The median PFS differed significantly (P = 0.03) between Group 1 (11 months) and Group 2 (28 months) at a median follow-up of 19.5 months. The 3-year OS was 28.6% and 57.1% in Group 1 and Group 2, respectively; and the median 3-year OS was 9 months (95% CI, 0.0–35.4) in Group 1, the median 3-year OS was unable to be calculated by SPSS 16.0 in Group 2 (4 out of 7 patients have survived), but the interval estimation were about 30.6–36.0 months, the average of 3-year OS was 33.3 months. However, there was no significant difference in both groups (P = 0.20). There were 9 PD, 6 SD, and 5 deaths in Group 1 but 8 PD, 11 SD, and 3 deaths in Group 2. The progressive diseases rates failed to show statistical significance: 60% and 42.1%. Median time to disease progression was 3 months in Group 1; however, the median time to disease progression was 11.5 months in Group 2. And stable disease lasting more than 12 months in both groups; however, the median time to stable disease was 16 and 20 months in Group 1 and Group 2, respectively. The AE rates were 66.7% (10/15) and 52.6% (10/19) in Group 1 and Group 2, respectively. Our findings demonstrated SU/SO in combination with DC-CIK could significantly prolong the PFS among patients with mRCC after radical nephrectomy, and the median time to disease progression and stable disease was prolonged to some extent. And 3-year OS was 1-fold in joint treatment group more than in SU/SO monotherapy group. SU/SO in combination with DC-CIK is likely to be a new approach for mRCC after radical nephrectomy. The baseline characteristics of patients are shown in [Table 2]. The side effects are shown in [Table 3]. The survival curves are shown in [Figure 1] and [Figure 2].
Table 2: Patients' baseline characteristics of pre-treatment and post-treatment in group 1 and 2

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Table 3: Adverse events of patients in Group 1 and 2

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Figure 1: Progression-free survival and 3-year overall survival of patients in Group 1 and 2. (a) Progression-free survival; (b) 3-year overall survival

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Figure 2: The comparisons of progression-free survival between Sorafenib in combination with dendritic cell-cytokine-induced killer and Sunitinib single agent

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The main AEs were bone marrow suppression (55.8%), oral ulcer (27.8%), fatigue (23.8%), and hand-foot syndrome (22.5%) in our study. Among two groups, there was 1 case developed serious AE (Grade III bone marrow suppression) in Group 1 and other patients in both groups whose AEs were in Grade I–II. The AE rate was 66.7% (10/15) in Group 1, and it was 52.6% (10/19) in Group 2, respectively. SU/SO in combination with DC-CIK could decrease AE rate.

The median PFS was 23.0 months in SO in combination with the DC-CIK group, and it was 6.0 months in SU monotherapy group. Despite the fact that the difference has reached 3-fold, there was no significant difference (P = 0.15). This phenomenon may relate to the change of DC function; researchers had proved SO could affect the function of DC.[7]


 > Discussion Top


Our study demonstrated that SU/SO in combination with DC-CIK could significantly prolong the median PFS, enhance the 3-year OS, prolong the median time to disease progression, and reduce the AE rates. PFS, 3-year OS, and AE seen in this study are better than those six trials reported in the past [Table 4].[12],[13],[14],[15],[16]
Table 4: The comparisons between this study and previous studies

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In our study, SU/SO in combination with DC-CIK prolonged PFS about 11–22 months, and 6.9–21.8 months in median 3-year OS than previous studies. In addition, there was only 1 case developed Grade III AE (Grade 3 bone suppression). There were 5 cases with 2 or more kinds of AE, and symptoms of AE were cured among those patients.

Moreover, the median time to disease progression was 3 months in Group 1, while it was 11.5 months in the Group 2 and 8.7 months in Motzer's study,[17] showing 8.5 months and 3 months improvement, respectively. The median time to stable disease was increased to 20 months in the patients receiving the combination of SU/SO plus DC-CIK, compared with 16 months for SU/SO single agent. The result demonstrated that the median time to disease progression was significantly prolonged in the patients receiving the combination of SU/SO plus DC-CIK; however, there was no obvious difference about the median time to stable disease in the patients.

In tumor microenvironment, the resistance to therapy of tumor cell was mediated by fibroblast, immune infiltrate, tumor vasculature, and so on.[18] Besides, the overexpression of hepatocyte growth factor in patients significantly correlated with therapeutic resistance.[19] Targeted drugs could reduce the level of immunosuppression induced by a tumor cell, improve the microenvironment, and enhance the level of myeloid-derived DC which correlates with PFS.[20],[21] The enhancement of microenvironment might correlate with changes of expression level for cytotoxic T-lymphocyte-associated antigen-4 or programmed death one ligand 1 (PD-L1). The study result indicated SU reduce the expression of PD-L1 on the surface of DC, restore function of T cells, and influence antitumor response from the immune system.[8],[22] Su also reduce neutrophil-to-lymphocyte ratio, which also correlates with PFS.[23]

CIK could improve patients' antitumor immunity by regulating the percentages of CD3+, CD8+, CD3+, and CD56+ cell as well as secretion of IFN-γ and TNF-α,[24] and significantly prolong the PFS of the patients after radical nephrectomy.[25] The OS has been prolonged up to 14.8–41.4 and 1 year survival has reached 82.8% among patients with mRCC treated by CIK therapy, and the level of myeloid-derived suppressor cells (MDSCs) has been reduced.[26] MDSC can inhibit effective T cells expansion, activation, and migration.[27] Importantly, MDSC-derived cytokines promote tumor angiogenesis, lead to resistance against treatment, and suppress antitumor immunity,[28],[29],[30] those results lead to the immune escape of tumor cell to some extent. Consequently, decrease the level of MDSC, which is the important initial step for immunotherapy, and the tumor growth is inhibited in vivo when the MDSC was treated with special peptibody.[31] SU decreased the level of MDSC and restored the function of T cells which was engaged in phospho-STAT3–dependent programming (pSTAT3+).[32] In our study, the observed efficacy possibly was changed microenvironment caused by joint therapy.

CIK immunotherapy can significantly improve the prognosis of metastatic clear cell RCC, and an increase of the cycle count can enhance beneficial response.[33] However, the antitumor cytotoxicity of CIK cells was reliant on DC modulation. A study showed that the antitumor cytotoxicity was significantly enhanced by the combination of CIK with SU-pretreated DC, and interestingly there was no significant effect between the direct exposure of CIK cells and SU.[8] We hypothesized that some or single protein on DC surface was changed by SU/SO, reducing the expression of the protein will improve the function of DC, and the DC enhanced the antitumor cytotoxicity of T lymphocytes and CIK cells.

We retrospective analyze the baseline characteristics in the patients and compared outcomes for the two approaches. Although the result indicated the improved efficacy, small samples and short follow-up lead to unavailability of 5-year OS. Randomized, prospective trial should be conducted, and the less clear mechanism about SU/SO in combination with DC-CIK in postoperative mRCC requires further investigation.

Financial support and sponsorship

The work was supported by The Capital Foundation For Clinical Application Research (Z15110004015010). Jie-Ping Wu Clinical Founation (320.6752.1203), the Specific Foundation Of Chinese Medical Association For Clinical Research (14020170544), Research Foundation of 307 Hospital (FC-2014-06 and ZH-2014-1).

Conflicts of interest

There are no conflicts of interest.

 
 > References Top

1.
Son HS, Jeon SH, Chang SG. Factors affecting the time to recurrence after radical nephrectomy for localized renal cell carcinoma. Korean J Urol 2013;54:744-9.  Back to cited text no. 1
[PUBMED]    
2.
Zisman A, Pantuck AJ, Belldegrun A. Immune and genetic therapies for advanced renal cell carcinoma. Rev Urol 2000;2:54-60.  Back to cited text no. 2
[PUBMED]    
3.
Patel PH, Chaganti RS, Motzer RJ. Targeted therapy for metastatic renal cell carcinoma. Br J Cancer 2006;94:614-9.  Back to cited text no. 3
[PUBMED]    
4.
Soerensen AV, Donskov F, Hermann GG, Jensen NV, Petersen A, Spliid H, et al. Improved overall survival after implementation of targeted therapy for patients with metastatic renal cell carcinoma: Results from the Danish Renal Cancer Group (DARENCA) study-2. Eur J Cancer 2014;50:553-62.  Back to cited text no. 4
[PUBMED]    
5.
Tang X, Liu T, Zang X, Liu H, Wang D, Chen H, et al. Adoptive cellular immunotherapy in metastatic renal cell carcinoma: A systematic review and meta-analysis. PLoS One 2013;8:e62847.  Back to cited text no. 5
[PUBMED]    
6.
Bedke J, Stenzl A. Immunotherapeutic strategies for the treatment of renal cell carcinoma: Where are we now? Expert Rev Anticancer Ther 2013;13:1399-408.  Back to cited text no. 6
[PUBMED]    
7.
Hipp MM, Hilf N, Walter S, Werth D, Brauer KM, Radsak MP, et al. Sorafenib, but not sunitinib, affects function of dendritic cells and induction of primary immune responses. Blood 2008;111:5610-20.  Back to cited text no. 7
[PUBMED]    
8.
Wongkajornsilp A, Wamanuttajinda V, Kasetsinsombat K, Duangsa-ard S, Sa-ngiamsuntorn K, Hongeng S, et al. Sunitinib indirectly enhanced anti-tumor cytotoxicity of cytokine-induced killer cells and CD3(+) CD56(+) subset through the co-culturing dendritic cells. PLoS One 2013;8:e78980.  Back to cited text no. 8
[PUBMED]    
9.
Schott M, Feldkamp J, Lettmann M, Simon D, Scherbaum WA, Seissler J. Dendritic cell immunotherapy in a neuroendocrine pancreas carcinoma. Clin Endocrinol (Oxf) 2001;55:271-7.  Back to cited text no. 9
[PUBMED]    
10.
Ren X, Yu J, Liu H, Zhang P, An X, Zhang N, et al. Th1 bias in PBMC induced by multicycles of auto-CIKs infusion in malignant solid tumor patients. Cancer Biother Radiopharm 2006;21:22-33.  Back to cited text no. 10
[PUBMED]    
11.
Li H, Wang C, Yu J, Cao S, Wei F, Zhang W, et al. Dendritic cell-activated cytokine-induced killer cells enhance the anti-tumor effect of chemotherapy on non-small cell lung cancer in patients after surgery. Cytotherapy 2009;11:1076-83.  Back to cited text no. 11
[PUBMED]    
12.
Hutson TE, Bukowski RM, Rini BI, Gore ME, Larkin JM, Figlin RA, et al. Efficacy and safety of sunitinib in elderly patients with metastatic renal cell carcinoma. Br J Cancer 2014;110:1125-32.  Back to cited text no. 12
[PUBMED]    
13.
Soerensen AV, Donskov F, Hermann GG, Jensen NV, Petersen A, Spliid H, et al. Improved overall survival after implementation of targeted therapy for patients with metastatic renal cell carcinoma: results from the Danish Renal Cancer Group (DARENCA) study-2. Eur J Cancer 2014;50:553-62.  Back to cited text no. 13
[PUBMED]    
14.
Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Oudard S, et al. Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma. J Clin Oncol 2009;27:3584-90.  Back to cited text no. 14
[PUBMED]    
15.
Motzer RJ, Bukowski RM. Targeted therapy for metastatic renal cell carcinoma. J Clin Oncol 2006;24:5601-8.  Back to cited text no. 15
[PUBMED]    
16.
Hagiwara M, Borker R, Oster G. Economic burden of adverse events in patients with metastatic renal cell carcinoma. Clin Ther 2013;35:1955-1963.e2.  Back to cited text no. 16
    
17.
Motzer RJ, Michaelson MD, Redman BG, Hudes GR, Wilding G, Figlin RA, et al. Activity of SU11248, a multitargeted inhibitor of vascular endothelial growth factor receptor and platelet-derived growth factor receptor, in patients with metastatic renal cell carcinoma. J Clin Oncol 2006;24:16-24.  Back to cited text no. 17
[PUBMED]    
18.
Junttila MR, de Sauvage FJ. Influence of tumour micro-environment heterogeneity on therapeutic response. Nature 2013;501:346-54.  Back to cited text no. 18
[PUBMED]    
19.
Straussman R, Morikawa T, Shee K, Barzily-Rokni M, Qian ZR, Du J, et al. Tumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretion. Nature 2012;487:500-4.  Back to cited text no. 19
[PUBMED]    
20.
Figlin RA. A novel personalized vaccine approach in combination with targeted therapy in advanced renal cell carcinoma. Immunotherapy 2014;6:261-8.  Back to cited text no. 20
[PUBMED]    
21.
van Cruijsen H, van der Veldt AA, Vroling L, Oosterhoff D, Broxterman HJ, Scheper RJ, et al. Sunitinib-induced myeloid lineage redistribution in renal cell cancer patients: CD1c dendritic cell frequency predicts progression-free survival. Clin Cancer Res 2008;14:5884-92.  Back to cited text no. 21
[PUBMED]    
22.
Nishioka Y, Aono Y, Sone S. Role of tyrosine kinase inhibitors in tumor immunology. Immunotherapy 2011;3:107-16.  Back to cited text no. 22
[PUBMED]    
23.
Kobayashi M, Kubo T, Komatsu K, Fujisaki A, Terauchi F, Natsui S, et al. Changes in peripheral blood immune cells: Their prognostic significance in metastatic renal cell carcinoma patients treated with molecular targeted therapy. Med Oncol 2013;30:556.  Back to cited text no. 23
[PUBMED]    
24.
Su X, Zhang L, Jin L, Ye J, Guan Z, Chen R, et al. Immunotherapy with cytokine-induced killer cells in metastatic renal cell carcinoma. Cancer Biother Radiopharm 2010;25:465-70.  Back to cited text no. 24
[PUBMED]    
25.
Zhang Y, Wang J, Wang Y, Lu XC, Fan H, Liu Y, et al. Autologous CIK cell immunotherapy in patients with renal cell carcinoma after radical nephrectomy. Clin Dev Immunol 2013;2013:195691.  Back to cited text no. 25
[PUBMED]    
26.
Wang Z, Zhang Y, Liu Y, Wang L, Zhao L, Yang T, et al. Association of myeloid-derived suppressor cells and efficacy of cytokine-induced killer cell immunotherapy in metastatic renal cell carcinoma patients. J Immunother 2014;37:43-50.  Back to cited text no. 26
[PUBMED]    
27.
Gabrilovich DI, Ostrand-Rosenberg S, Bronte V. Coordinated regulation of myeloid cells by tumours. Nat Rev Immunol 2012;12:253-68.  Back to cited text no. 27
[PUBMED]    
28.
Folkman J. Tumor angiogenesis: Therapeutic implications. N Engl J Med 1971;285:1182-6.  Back to cited text no. 28
[PUBMED]    
29.
Kerbel RS. Tumor angiogenesis. N Engl J Med 2008;358:2039-49.  Back to cited text no. 29
[PUBMED]    
30.
Schmid MC, Varner JA. Myeloid cells in the tumor microenvironment: Modulation of tumor angiogenesis and tumor inflammation. J Oncol 2010;2010:201026.  Back to cited text no. 30
[PUBMED]    
31.
Qin H, Lerman B, Sakamaki I, Wei G, Cha SC, Rao SS, et al. Generation of a new therapeutic peptide that depletes myeloid-derived suppressor cells in tumor-bearing mice. Nat Med 2014;20:676-81.  Back to cited text no. 31
[PUBMED]    
32.
Finke JH, Rayman PA, Ko JS, Bradley JM, Gendler SJ, Cohen PA. Modification of the tumor microenvironment as a novel target of renal cell carcinoma therapeutics. Cancer J 2013;19:353-64.  Back to cited text no. 32
[PUBMED]    
33.
Liu L, Zhang W, Qi X, Li H, Yu J, Wei S, et al. Randomized study of autologous cytokine-induced killer cell immunotherapy in metastatic renal carcinoma. Clin Cancer Res 2012;18:1751-9.  Back to cited text no. 33
[PUBMED]    


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