Kidney autotransplantation for the treatment of renal artery occlusion after endovascular aortic repair: a case report.

BACKGROUND: Unintentional renal artery occlusion after endovascular aneurysm repair (EVAR) for abdominal aortic aneurysm remains one of the most unfavorable complications. Renal salvage options include percutaneous transluminal renal artery angioplasty (PTRA) and open hepatosplenorenal bypass. However, the usefulness of kidney autotransplantation (AutoTx) remains unclear. CASE PRESENTATION: A 76-year-old woman with a right solitary kidney attributable to a left renal thromboembolism had previously undergone EVAR with a stent graft for an infrarenal aortic aneurysm, which led to ostial occlusion of the right renal artery. In addition, she had undergone PTRA and stenting. Two days before admission, she developed leg edema and hypertension, leading her to visit the hospital. Her serum creatinine level was 2.4 (baseline, 1.0) mg/dL. Acute kidney injury due to renal artery in-stent restenosis was suspected; re-angioplasty was attempted on day 2 of hospitalization, but was unsuccessful. Her renal function did not improve and anuria persisted; thus, hemodialysis was initiated on the same day. The right kidney size (8.6 cm) was preserved relative to her body size, with only mild cortical atrophy. Doppler ultrasonography and mercaptoacetyltriglycine scintigraphy revealed minimal but significant perfusion of the right kidney. Therefore, we considered that kidney perfusion was sustained and renal function could be reversed. On day 25 of hospitalization, right kidney AutoTx to the right iliac fossa was performed to reestablish adequate renal perfusion and reverse the need for dialysis. Soon after the procedure, the patient started passing urine. Her renal function improved; her serum creatinine level decreased to 1.0 mg/dL on day 33 of hospitalization. Hemodialysis was discontinued after the surgery. Zero-hour kidney biopsy showed only mild tubular injury, with neither tubular necrosis nor glomerular abnormalities. CONCLUSIONS: Kidney AutoTx can be performed for patients with renal artery in-stent occlusion after unsuccessful PTRA who previously underwent EVAR. Our case showed successful recovery of renal function nearly 1 month after renal artery occlusion, indicating that revascularization should be considered even if it is delayed, as the kidney might be perfused through collateral circulation.

Circulating miRNA panels for specific and early detection in bladder cancer.

Bladder cancer is the 9th leading cause of cancer death worldwide. The major problem in bladder cancer is primarily the high recurrence rate after drug treatment and resection. Although conventional screening methods, such as cystoscopy, urinary cytology and ultrasound sonography, have become widely used in clinical settings, the diagnostic performance of these modalities is unsatisfactory due to low accuracy or high invasiveness. Because circulating micro RNA (miRNA) profiles have recently been reported as an attractive tool for liquid biopsy in cancer screening, here, we performed global miRNA profiling of 392 serum samples of bladder cancer patients with 100 non-cancer samples and 480 samples of other types of cancer as controls. We randomly classified the bladder cancer and control samples into 2 cohorts, a training set (N = 486) and a validation set (N = 486). By comparing both controls, we identified specific miRNA, such as miR-6087, for diagnosing bladder cancer in the training and validation sets. Furthermore, we found that a combination of 7 miRNA (7-miRNA panel: miR-6087, miR-6724-5p, miR-3960, miR-1343-5p, miR-1185-1-3p, miR-6831-5p and miR-4695-5p) could discriminate bladder cancer from non-cancer and other types of tumors with the highest accuracy (AUC: .97; sensitivity: 95%; specificity: 87%). The diagnostic accuracy was high, regardless of the stage and grade of bladder cancer. Our data demonstrated that the 7-miRNA panel could be a biomarker for the specific and early detection of bladder cancer.

Early post-transplant diagnosis of cytomegalovirus esophagitis in an ABO-incompatible kidney transplant recipients: A case report.

Cytomegalovirus (CMV) is a common infectious pathogen in kidney transplant patients. Here, we present a case of CMV esophagitis with antigenemia, that developed within 3 days of kidney transplantation, a timeline generally considered to be too early for development of a CMV infection. Intense immunosuppressive therapy for desensitization in ABO-incompatibility or in the presence of donor-specific antibody can increase the risk for significant opportunistic infection immediately after or even before transplantation.

Hemorrhagic shock due to bleeding from an arteriovenous fistula after allograft biopsy in a kidney transplant recipient: a case report.

Arteriovenous fistula (AVF) after allograft biopsy occurs in 1.6-8.3% of kidney transplant patients and most cases remain asymptomatic. Here, we report a case of hemorrhagic shock in a kidney transplant recipient following bleeding from an AVF after graft biopsy. Immediate intensive care including angiographic embolization saved the patient and the allograft. A 62-year-old woman with end-stage renal disease caused by diabetic nephropathy underwent ABO-incompatible kidney transplantation. No complications occurred in the early postoperative period. However, serum creatinine levels did not decrease sufficiently and decreased graft diastolic blood flow was noted on ultrasound. Therefore, at 14 days after kidney transplantation, allograft biopsy was performed to elucidate the cause of allograft dysfunction. At 5 days after allograft biopsy, the patient developed hemorrhagic shock caused by bleeding from an AVF in the allograft. We immediately performed angiographic embolization, and her vital signs improved without deterioration in renal function. AVF can cause hemorrhagic shock, and angiographic embolization is effective for treating it.

A bioinformatics-to-clinic sequential approach to analysis of prostate cancer biomarkers using TCGA datasets and clinical samples: a new method for precision oncology?

Biomarker-driven cancer therapy has met with significant clinical success. Identification of a biomarker implicated in a malignant phenotype and linked to poor clinical outcome is required if we are to develop these types of therapies. A subset of prostate adenocarcinoma (PACa) cases are treatment-resistant, making them an attractive target for such an approach. To identify target molecules implicated in shorter survival of patients with PACa, we established a bioinformatics-to-clinic sequential analysis approach, beginning with 2-step in silico analysis of a TCGA dataset for localized PACa. The effect of candidate genes identified by in silico analysis on survival was then assessed using biopsy specimens taken at the time of initial diagnosis of localized and metastatic PACa. We identified PEG10 as a candidate biomarker. Data from clinical samples suggested that increased expression of PEG10 at the time of initial diagnosis was linked to shorter survival time. Interestingly, PEG10 overexpression also correlated with expression of chromogranin A and synaptophysin, markers for neuroendocrine prostate cancer, a type of treatment-resistant prostate cancer. These results indicate that PEG10 is a novel biomarker for shorter survival of patients with PACa. Also, PEG10 expression at the time of initial diagnosis may predict focal neuroendocrine differentiation of PACa. Thus, PEG10 may be an attractive target for biomarker-driven cancer therapy. Thus, bioinformatics-to-clinic sequential analysis is a valid tool for identifying targets for precision oncology.

Serum Aberrant N-Glycan Profile as a Marker Associated with Early Antibody-Mediated Rejection in Patients Receiving a Living Donor Kidney Transplant.

We determined if the serum N-glycan profile can be used as a diagnostic marker of antibody-mediated rejection (ABMR) in living donor kidney transplant (LKTx) recipients. Glycoblotting, combined with mass spectrometry, was used to retrospectively examine N-glycan levels in the postoperative sera of 197 LKTx recipients of whom 16 recipients had ABMR with or without T-cell-mediated rejection (TCMR), 40 recipients had TCMR, and 141 recipients had no adverse events. Multivariate discriminant analysis for prediction of ABMR was performed by inputting an ABMR event as an explanatory variable and sex, age, and serum N-glycan level as objective variables. The N-glycan score was calculated by multiplying the level of candidate objective variables by objective function values. The ABMR predictive performance of the N-glycan score was assessed by receiver operator characteristic curve and Kaplan-Meier curve analyses. The N-glycan score discriminated ABMR with 81.25% sensitivity, 87.85% specificity, and an area under the curve (AUC) of 0.892 that was far superior to that of preformed donor-specific antibody status (AUC, 0.761). Recipients with N-glycan-positive scores >0.8770 had significantly shorter ABMR survival than that of recipients with N-glycan-negative scores. Although the limitations of our study includ its small sample size and retrospective nature, the serum N-glycan score may contribute to prediction of ABMR.

Embryonic kidney function in a chronic renal failure model in rodents.

BACKGROUND: Rapid advancements have been made in alternative treatments for renal diseases. Our goal for renal regeneration is to establish a kidney graft derived from human embryonic tissues. In this study, we investigated the effects of host renal failure on the structure and activity of transplanted embryonic kidney and bladder, and found that diuretics effectively induced urine production in the transplanted kidney. METHODS: Uremic conditions were reproduced using a 5/6 renal infarction rat model. An embryonic kidney plus bladder (embryonic day 15) was isolated from a pregnant Lewis rat and transplanted into the para-aortic area of a 5/6 renal-infarcted Lewis rat. Following growth, the embryonic bladder was successfully anastomosed to the host ureter. RESULTS: We assessed graft function in terms of survival rates and found no differences between normal (n = 5) and renal failure (n = 8) groups (median survival: 70.5 vs 74.5 h; p = 0.331) in terms of survival, indicating that the grafts prolonged rat survival, even under renal failure conditions. Furosemide (n = 9) significantly increased urine volume compared with saline-treated controls (n = 7; p < 0.05), confirming that the grafts were functional. We also demonstrated the possibilities of an in vivo imaging system for determining the viability of transplanted embryonic kidney with bladder. CONCLUSION: The results of this study demonstrate that transplanted embryonic kidney and bladder can grow and function effectively, even under uremic conditions.

A Prospective Randomized, Comparative Trial of High-Dose Mizoribine Versus Mycophenolate Mofetil in Combination With Tacrolimus and Basiliximab for Living Donor Renal Transplant: A Multicenter Trial.

OBJECTIVES: Our objectives were to compare the clinical outcomes of mizoribine (12 mg/kg/d) and mycophenolate mofetil (2000 mg/d) in combination with tacrolimus, basiliximab, and corticosteroids. MATERIALS AND METHODS: We enrolled 83 recipients of living-donor renal transplant (performed between 2008 and 2013) in this study. This prospective multi-institutional randomized comparative study compared mizoribine (n = 41) and mycophenolate mofetil (n = 42) in combination with tacrolimus, basiliximab, and corticosteroids for living-donor renal transplant recipients. We compared the acute rejection and graft survival rates and adverse event rates within 1 year of renal transplant between the 2 groups using intention-to-treat analyses. RESULTS: During the 1-year observation period, patient and graft survival rates were 100%. The acute rejection rate was 17.1% in the mizoribine group and 19% in the mycophenolate mofetil group. The incidence rate of cytomegalovirus infection seropositivity (recipient and donor with positive cytomegalovirus antibody status) was higher in the mycophenolate mofetil group than in the mizoribine group, although the difference in these rates was not statistically significant. The incidence of leukopenia was higher in the mizoribine group than in the mycophenolate mofetil group. CONCLUSIONS: High-dose mizoribine at 12 mg/kg/day was a safe and efficacious immunosuppressive alternative to mycophenolate mofetil in living-donor renal transplant recipients. Leukopenia should be closely monitored in the initial period of insufficient kidney function after renal transplant.

Paraneoplastic Dermatomyositis Associated with Metastatic Seminoma.

We report the first case in Japan of paraneoplastic dermatomyositis with pure seminoma, a tumor that extremely rarely accompanies dermatomyositis. The patient presented to the hospital with muscle weakness and erythema and was diagnosed with dermatomyositis from skin biopsy. Routine radiological screening revealed testicular tumor and massive lymph node metastases. We initially performed orchiectomy along with conventional immunotherapy. However, muscle weakness gradually worsened, and he eventually showed dysphagia and forced respiration and became bedridden. Although he seemed close to being too unstable to tolerate further treatment, we started carefully adjusted chemotherapy comprising 4 courses of etoposide plus cisplatin, which proved highly successful. Lymph node metastases completely disappeared and swallowing and respiration fully normalized after completing chemotherapy. We believe that this clinical success was due to our decision to initiate chemotherapy even in such a weak patient.

A Prospective Randomized, Comparative Trial of High-Dose Mizoribine Versus Mycophenolate Mofetil in Combination With Tacrolimus and Basiliximab for Living Donor Renal Transplant: A Multicenter Trial.

OBJECTIVES: Our objectives were to compare the clinical outcomes of mizoribine (12 mg/kg/d) and mycophenolate mofetil (2000 mg/d) in combination with tacrolimus, basiliximab, and corticosteroids. MATERIALS AND METHODS: We enrolled 83 recipients of living-donor renal transplant (performed between 2008 and 2013) in this study. This prospective multi-institutional randomized comparative study compared mizoribine (n = 41) and mycophenolate mofetil (n = 42) in combination with tacrolimus, basiliximab, and corticosteroids for living-donor renal transplant recipients. We compared the acute rejection and graft survival rates and adverse event rates within 1 year of renal transplant between the 2 groups using intention-to-treat analyses. RESULTS: During the 1-year observation period, patient and graft survival rates were 100%. The acute rejection rate was 17.1% in the mizoribine group and 19% in the mycophenolate mofetil group. The incidence rate of cytomegalovirus infection seropositivity (recipient and donor with positive cytomegalovirus antibody status) was higher in the mycophenolate mofetil group than in the mizoribine group, although the difference in these rates was not statistically significant. The incidence of leukopenia was higher in the mizoribine group than in the mycophenolate mofetil group. CONCLUSIONS: High-dose mizoribine at 12 mg/kg/day was a safe and efficacious immunosuppressive alternative to mycophenolate mofetil in living-donor renal transplant recipients. Leukopenia should be closely monitored in the initial period of insufficient kidney function after renal transplant.

Expression Level of Urinary MicroRNA-146a-5p Is Increased in Patients With Bladder Cancer and Decreased in Those After Transurethral Resection.

BACKGROUND: Bladder cancer is the most prevalent malignancy involving the urinary system and exhibits a markedly high recurrence rate. Therefore, reliable and noninvasive diagnostic and surveillance methods are desperately needed. PATIENTS AND METHODS: Candidate microRNAs (miRNAs) were selected from the miRNAs that were differentially expressed in bladder cancer cell lines (T24 and RT4) compared to normal ureteral epithelial tissue using miRNA-microarray analysis. The candidate miRNAs were validated by quantitative reverse transcription polymerase chain reaction assay using voided urine samples. RESULTS: We identified 3 miRNAs (miR-301b, -563, and -146a-5p) that demonstrated > 2-fold higher expression levels in cancer cell lines than in the normal ureteral epithelial tissue. Of these, only miR-146a-5p was consistently and significantly higher in urine samples from the patients with bladder cancer than in those from the normal individuals (P = .0014). The patients with high-grade tumors exhibited significantly higher urinary miR-146a-5p levels than those with low-grade tumors, and the patients with invasive tumors tended to show higher urinary miR-146a-5p levels than those with noninvasive tumors. Elevated urinary miR-146a-5p levels in patients with bladder cancer were decreased to the normal level after transurethral resection of the tumors (P = .0214). CONCLUSION: Our study suggested that urinary miR-146a-5p might be useful as a new noninvasive diagnostic marker, therapeutic target, or anticancer agent for bladder cancer, as well as for increasing our understanding of cancer biology.

Solitary Fibrous Tumor of the Kidney Developing Local Recurrence.

Solitary fibrous tumor (SFT) of the kidney is a rare entity and usually displays a favorable prognosis. We herein report a second case of renal SFT developing local recurrence. A 50-year-old man was referred to our hospital because of a left renal mass. An abdominal CT detected a large renal tumor and radical nephrectomy was performed with a possible diagnosis of renal cell carcinoma. The resected tumor size was measured at 17 × 11 × 8 cm. Grossly, necrosis was observed in central lesion of the tumor but hemorrhage was not observed. Microscopically, the tumor consisted of spindle-shaped cells with scant cytoplasm accompanied by hyalinized collagenous tissue, which displayed hemangiopericytomatous patterns. The cellularity was normal and nuclear pleomorphism was not observed. Ki-67 labeling index was less than 3%. The pathological diagnosis of SFT was made without obvious malignant findings. Three years after the surgery, a follow-up CT scan detected a mass lesion in the tumor bed. Surgical resection was performed and the resected tumor was compatible with local recurrence of the SFT without obvious malignant findings. Renal SFT should be carefully monitored even in the absence of obvious malignant findings.

Pharmacokinetic analysis of cyclosporine in a renal transplant recipient with congenital absence of the portal vein.

Here we report therapeutic drug monitoring of cyclosporine in a kidney transplant recipient lacking enterohepatic circulation. The patient developed steroid-resistant nephrotic syndrome at age 14 years, and was medicated with an oral cyclosporine microemulsion. However, her cyclosporine trough level was unexpectedly elevated, and subsequent investigations showed that she was deficient in drug metabolism as a result of the congenital absence of the portal vein. Her renal function gradually decreased and she became dialysis-dependent at the age of 21 years, and kidney transplantation was planned. Based on pretransplant therapeutic drug monitoring, we started cyclosporine microemulsion at half of the conventional dosage. After transplantation, the dosage was successfully adjusted to achieve a target trough level. The post-transplant course was stable with no symptoms of rejection or cyclosporine-associated nephrotoxicity.

Subcutaneous pathway diversion for peritoneal dialysis catheter salvage.

Peritoneal dialysis (PD) catheter-related infection is still is the most troublesome problem for continuation of PD without the need to switch to hemodialysis. We have been performing subcutaneous pathway diversion (SPD) as a surgical treatment for refractory exit-site and tunnel infection (ESTI). To clarify the efficacy and safety of SPD, we conducted a retrospective study. From August 2008 to August 2013, 30 SPDs were performed in 26 patients (16 men, 10 women; mean age: 58 +/- 13 years; 54% with diabetes; mean body mass index: 23.9 +/- 3.5 kg/ m2). The reasons for the SPDs were ESTI in 25 patients, and outer cuff extrusion in 1 patient. All patients resumed PD immediately after SPD, and the duration of hospitalization was 11.7 +/- 10.1 days. After SPD, one patient experienced a dialysate leak, and another patient experienced a mild subcutaneous hematoma. Another 4 patients developed exit-site infection (ESI) and underwent a second SPD. Of those 4 patients, 3 presented with another ESI unrelated to the first episode, and all developed an ESI after 6 months or more. The remaining 20 patients experienced no such complications. Furthermore, catheter survival after SPD was 17.4 +/- 13.4 months. To eradicate ESTTI we suggest that SPD, which does not require catheter removal or interruption of PD, is useful compared with the unroofing technique or catheter removal.

Induction of macrophage-like immunosuppressive cells from mouse ES cells that contribute to prolong allogeneic graft survival.

Recent progress in regenerative medicine has enabled the utilization of pluripotent stem cells (PSCs) such as embryonic stem cells (ESCs) as a donor resource for transplantation. However, immune suppression is still needed when the donor-recipient combination is allogeneic. Protection of ESCs-derived grafts from host immune response might be achieved thought the utilization of immunosuppressive cells generated from ESCs. In the present study, we show that a certain fraction of immunosuppressive cells can be generated from ESCs and help to suppress immune response against allogeneic grafts. ESCs-derived suppressor cells (ES-SCs) resembled macrophages in terms of cell surface molecule and gene expressions. Furthermore, gene expression analysis including microarray showed that ES-SCs have M1/M2 hybrid phenotype with high expression of genes correlated to immunosuppression of T cell response. Indeed, ES-SCs were effective to block allogeneic T cell proliferation in a nitric oxide-dependent manner, and prolonged the survival of ESCs-derived embryoid bodies or cardiomyocytes grafts transplanted into mouse kidney capsule. Thus, we consider the potential use of these ESCs-derived macrophage-like immunosuppressive cells as cellular therapies to promote long-term graft survival in future therapies.

Asymptomatic post-transplant lymphoproliferative disorder diagnosed at one year protocol renal allograft biopsy.

Post-transplant lymphoproliferative disorder (PTLD) is a neoplastic complication with a potentially fatal outcome that develops as a consequence of immunosuppression, and is mainly associated with Epstein-Barr virus (EBV) infection. A 70-year-old woman underwent a live unrelated, ABO-incompatible renal transplant for end-stage renal disease. One year after transplantation, protocol biopsy revealed pathological changes indicative of the histological subtype of 'early lesions of PTLD' according to the World Health Organization classification, while the patient showed no clinical signs or symptoms. The patient was finally diagnosed with EBV-positive PTLD by in situ hybridization for EBER (EBV-encoded RNA), and was successfully treated based on the reduction of immunosuppression. Protocol biopsy within the first post-transplant year is the only diagnostic measure to detect asymptomatic early PTLD, which allows for early intervention and leads to better outcomes.

Suppression of Tregs by anti-glucocorticoid induced TNF receptor antibody enhances the antitumor immunity of interferon-α gene therapy for pancreatic cancer.

We have reported that interferon (IFN)-α can attack cancer cells by multiple antitumor mechanisms including the induction of direct cancer cell death and the enhancement of an immune response in several pancreatic cancer models. However, an immunotolerant microenvironment in the tumors is often responsible for the failure of the cancer immunotherapy. Here we examined whether the suppression of regulatory T cells (Tregs) within tumors can enhance an antitumor immunity induced by an intratumoral IFN-α gene transfer. First we showed that an intraperitoneal administration of an agonistic anti-glucocorticoid induced TNF receptor (GITR) monoclonal antibody (mAb), which is reported to suppress the function of Tregs, significantly inhibited subcutaneous tumor growth in a murine pancreatic cancer model. The anti-GITR mAb was then combined with the intratumoral injection of the IFN-α-adenovirus vector. The treatment with the antibody synergistically augmented the antitumor effect of IFN-α gene therapy not only in the vector-injected tumors but also in the vector-uninjected tumors. Immunostaining showed that the anti-GITR mAb decreased Foxp3(+) cells infiltrating in the tumors, while the intratumoral IFN-α gene transfer increased CD4(+) and CD8(+) T cells in the tumors. Therefore, the combination therapy strongly inclined the immune balance of the tumor microenvironment in an antitumor direction, leading to a marked systemic antitumor effect. The CCR5 expression on Tregs was downregulated in the antibody-treated mice, which may explain the decrease of tumor-infiltrating Tregs. The combination of Treg-suppression by GITR mAb and the tumor immunity induction by IFN-α gene therapy could be a promising therapeutic strategy for pancreatic cancer.

Risk factors associated with inadequate veins for placement of arteriovenous fistulas for hemodialysis.

An arteriovenous fistula (AVF) between the radial artery and cephalic vein at the wrist is the preferred type of hemodialysis vascular access. However, in the practice of access placement, we are aware that some patients fail to form the standard forearm radial-cephalic AVF, owing to naturally small veins or acquired abnormal lesions of the veins. To identify the risk factors for failure to form the standard AVF, we examined 305 consecutive patients who underwent first-time access surgery at our hospital from January 2006 to December 2010. We compared the patients' characteristics between those having normal vessels and successfully forming the standard AVF, and those having apparently abnormal vessels and thus forming alternative types of access instead. Histories of major and minor surgery were specifically evaluated, assuming that surgical procedures in the past could potentially damage the superficial veins. We created 207 standard and 98 alternative accesses during the period and found that significantly more patients with alternative accesses (31 %) had undergone major surgery of a variety of specialties, in comparison with those with the standard AVF (15.0 %). Multivariate logistic analysis revealed that a history of major surgery (OR = 2.39, 95 %CI 1.29-4.47, p = 0.006) and female gender (OR = 1.87, 95 %CI 1.10-3.20, p = 0.02) were independent risk factors associated with failure to construct the standard AVF. Our results indicate that previous surgery can damage the superficial veins and cause venous abnormality, which makes construction of the standard AVF difficult. We propose that care should be taken to preserve the superficial veins when patients for whom dialysis therapy is a future possibility undergo surgical procedures, especially invasive ones.

Vascular endothelial growth factor-D-mediated blockade of regulatory T cells within tumors is induced by hematopoietic stem cell transplantation.

Lymphopenia-induced homeostatic proliferation of T cells after autologous hematopoietic stem cell transplantation (HSCT) skews the T cell repertoire by engaging tumor-associated Ags, leading to an induction of antitumor immunity. However, how HSCT alters the immunosuppressive microenvironment in the tumors is unknown. In this study, we first analyzed the kinetics of regulatory T cells (Tregs) in the tumors after syngeneic HSCT. Unexpectedly, the frequency of CD4⁺ cells expressing Foxp3 was increased in the spleens, whereas the frequency was clearly decreased in the tumors after HSCT. The origin of reconstituted CD4⁺ and Foxp3⁺ cells in the tumors was mainly from the expansion of transferred splenic T cells. Then, to examine the mechanism of Treg suppression after HSCT, we isolated CD11c⁺ cells from tumors. A large amount of Treg-inhibitory cytokine IL-6 was secreted from the CD11c⁺ cells in the tumors, but not in the spleens in the recipient mice. Furthermore, to understand what factor affects the activity of CD11c⁺ cells in the tumors after HSCT, we analyzed the expression of various cytokines/chemokines with mouse cytokine Ab arrays, and noticed that VEGF-D concentration was increased in the tumors in the early period after HSCT. The CD11c⁺ cells produced IL-6 in response to VEGF-D stimulation, and an administration of VEGF receptor-3 neutralizing Ab significantly suppressed the production of IL-6 from CD11c⁺ cells accompanied with the increase of Tregs in the tumors of HSCT recipients. Autologous HSCT creates an environment that strongly supports the enhancement of antitumor immunity in reconstituted lymphopenic recipients through the suppression of Tregs.