Purpose To evaluate the clinical and immunologic outcomes of DC (dendritic cell) vaccine with interleukin (IL)-2 and IFN-α 2a in metastatic renal cell carcinoma patients. Experimental Design Eighteen consented and eligible patients were treated. Peripheral blood monocytes were cultured ex vivo into mature DCs and loaded with autologous tumor lysate. Treatment consisted of five cycles of intranodal vaccination of DCs (1 × 107 cells/1 mL Lactated Ringer’s solution), 5-day continuous i.v. infusion of IL-2 (18MiU/m2), and three s.c. injections of IFN-α 2a (6MiU) every other day. Response Evaluation Criteria in Solid Tumors criteria were used for disease assessment. Correlative immunologic end points included peripheral blood lymphocyte cell phenotype and function as well as peripheral blood anti–renal cell carcinoma antibody and cytokine levels. Results All patients received between two and five treatment cycles. Toxicities consisted of known and expected cytokine side effects. Overall objective clinical response rate was 50% with three complete responses. Median time to progression for all patients was 8 months, and median survival has not been reached (median follow up of 37+ months). Treatment-related changes in correlative immunologic end points were noted and the level of circulating CD4+ T regulatory cells had a strong association with outcome. Pre–IP-10 serum levels approached significance for predicting outcome. Conclusions The clinical and immunologic responses observed in this trial suggest an interaction between DC vaccination and cytokine therapy. Our data support the hypothesis that modulation of inflammatory, regulatory, and angiogenic pathways are necessary to optimize therapeutic benefit in renal cell carcinoma patients. Further exploration of this approach is warranted.

high score lesions. There was no statistically significant difference in the demographics of the three groups.• There was a significant difference in warm ischaemia time (16 vs 23 vs 31 min; P < 0.001), estimated blood loss (163 vs 312 vs 317 mL; P = 0.034) and length of hospital stay (1.2 vs 1.9 vs 2.3 days; P < 0.001) between the low, intermediate and high score groups, respectively. There was no difference in overall operative time ( P = 0.862), transfusion rate ( P = 0.665), complication rate ( P = 0.419), preoperative creatinine clearance ( P = 0.888) or postoperative creatinine clearance ( P = 0.473) between the groups.• Sixty-one lesions (43%) were anterior and 80 (57%) were posterior. No difference was found among any intra-operative, pathological or postoperative outcomes when comparing anterior vs posterior lesions. CONCLUSIONS• In patients undergoing LPN, a higher RNS was significantly associated with an increased estimated blood loss, warm ischaemia time and length of hospital stay.• The RNS may stratify tumours based on the technical difficulty of performing LPN. What's known on the subject? and What does the study add? For small renal tumours, partial nephrectomy provides excellent cancer control and preserves renal function. The RENAL Nephrometry Score is useful for quantifying anatomic features relevant to surgical decision-making.In patients undergoing laparoscopic partial nephrectomy, this study shows a correlation between RENAL Nephrometry Score and estimated blood loss, warm ischemia time, and length of hospital stay, suggesting that the RENAL Nephrometry Score may be useful for predicting the technical challenge posed by a renal tumour. OBJECTIVE• To assess the use of the RENAL Nephrometry Score (RNS), which has been proposed as an anatomical classification system for renal masses, aiming to predict surgical outcomes for patients undergoing laparoscopic partial nephrectomy (LPN). MATERIALS AND METHODS• In the present study, 159 consecutive patients who underwent LPN were reviewed and RNS was calculated for 141 patients with solitary renal masses who had complete radiographic data.• Renal tumours were categorized by RNS as low (nephrometry sum 4-6), intermediate (sum 7-9) and high (sum 10-12). RESULTS• Of the 141 patients, there were 43 (30%) low, 91 (65%) intermediate and seven (5%)

Purpose While stereotactic body radiation therapy (SBRT) can reduce tumor volumes in metastatic renal cell carcinoma (mRCC) patients, little is known regarding the immunomodulatory effects of high-dose radiation in the tumor microenvironment. The main objectives of this pilot study were to assess the safety and feasibility of nephrectomy following SBRT treatment of mRCC patients and analyze the immunological impact of high-dose radiation. Experimental Design Human RCC cell lines were irradiated and evaluated for immunomodulation. In a single-arm feasibility study, mRCC patients were treated with 15 Gray (Gy) SBRT at the primary lesion in a single fraction followed 4 weeks later by cytoreductive nephrectomy. RCC specimens were analyzed for tumor-associated antigen (TAA) expression and T cell infiltration. The trial has reached accrual (ClinicalTrials.gov identifier: NCT01892930). Results RCC cells treated in vitro with radiation had increased TAA expression compared to untreated tumor cells. Fourteen patients received SBRT followed by surgery and treatment was well tolerated. SBRT-treated tumors had increased expression of the immunomodulatory molecule calreticulin and TAA (CA9, 5T4, NY-ESO-1, and MUC-1). Ki67+ proliferating CD8+ T cells and FOXP3+ cells were increased in SBRT-treated patient specimens in tumors and at the tumor-stromal interface compared with archived patient specimens. Conclusions It is feasible to perform nephrectomy following SBRT with acceptable toxicity. Following SBRT, patient RCC tumors have increased expression of calreticulin, TAA, as well as a higher percentage of proliferating T cells compared to archived RCC tumors. Collectively, these studies provide evidence of immunomodulation following SBRT in mRCC.

We quantitatively evaluated dendritic cell (DC) infiltration in primary colorectal cancers from 44 patients and metastatic colorectal tumors from 13 patients using immunohistochemistry for the DC marker CD83, HLA-DR, and the DC activation molecules CD40 and CD86. Nearly all CD83+ cells were also HLA-DR+, CD40+, and CD86+, indicating that the DCs that infiltrate colon cancer in vivo express the activation and costimulatory molecules associated with a mature DC phenotype. The density of DCs in colorectal cancer primaries was three times lower than that seen in normal colonic mucosa (0.29 versus 0.84 CD83+ cells/ high-power field (hpf), p < 0.001). Dendritic cells were rarely observed in metastatic tumors: DC density in metastases was sixfold lower than in colorectal primary tumors (0.05 versus 0.29 CD83+ cells/hpf, p < 0.001). Because cytokines have been shown, in vitro, to exert potent effects on DCs, we also evaluated the relationship between intratumor DC density and the expression of cytokines by tumor-infiltrating lymphocytes (TILs) and tumor cells. Expression of interleukin-10 and transforming growth factor beta by either TIL or tumor cells was not associated with decreased DC density or decreased expression of CD40 or CD86 on DCs. Tumor expression of vascular endothelial growth factor was associated with a more than twofold increase in DC density (p = 0.01). Patients who had a high proportion of TILs expressing tumor necrosis factor (TNF) had a greater intratumor mature DC density than patients with a low proportion of TNF + TIL (0.54 versus 0.21 CD83+ cells/hpf, p < 0.01).