Autoreactive T cells target peripheral nerves in Guillain-Barré syndrome.

Guillain-Barré syndrome (GBS) is a rare heterogenous disorder of the peripheral nervous system, which is usually triggered by a preceding infection, and causes a potentially life-threatening progressive muscle weakness1. Although GBS is considered an autoimmune disease, the mechanisms that underlie its distinct clinical subtypes remain largely unknown. Here, by combining in vitro T cell screening, single-cell RNA sequencing and T cell receptor (TCR) sequencing, we identify autoreactive memory CD4+ cells, that show a cytotoxic T helper 1 (TH1)-like phenotype, and rare CD8+ T cells that target myelin antigens of the peripheral nerves in patients with the demyelinating disease variant. We characterized more than 1,000 autoreactive single T cell clones, which revealed a polyclonal TCR repertoire, short CDR3ß lengths, preferential HLA-DR restrictions and recognition of immunodominant epitopes. We found that autoreactive TCRß clonotypes were expanded in the blood of the same patient at distinct disease stages and, notably, that they were shared in the blood and the cerebrospinal fluid across different patients with GBS, but not in control individuals. Finally, we identified myelin-reactive T cells in the nerve biopsy from one patient, which indicates that these cells contribute directly to disease pathophysiology. Collectively, our data provide clear evidence of autoreactive T cell immunity in a subset of patients with GBS, and open new perspectives in the field of inflammatory peripheral neuropathies, with potential impact for biomedical applications.

[Living-donor robotic-assisted kidney transplantation: French academic center experience]. / Transplantation rénale robot-assistée avec donneur vivant : expérience d'un centre universitaire français.

INTRODUCTION: The main objective was to report the intra-, post-operative and functional outcomes of living-donor robotic-assisted kidney transplantation (RAKT), performed by a surgeon skilled in robotic surgery. The secondary objective was to compare the results of RAKT, based on the surgeon's experience. METHODS: For this retrospective cohort study, we analyzed data from consecutive patients who underwent living-donor RAKT from July 2015 to March 2020 and compared the results of RAKT according to the surgeon's experience (group 1: 1-14th RAKT versus group 2: 15-29th RAKT). RESULTS: Twenty-nine living-donor RAKT were performed. The median age and BMI of the recipients were: 57.0 (44.0-66.0) years and 32.7 (23.5-39.6)kg/m2. The median overall operative time and median console time were: 140.0 (122.5-165.0) and 120.0 (107.5-137.5) minutes. The median rewarming time, arterial, venous and urinary anastomoses durations were: 35.0 (27.5-45.0), 15.0 (11.0-20.0), 12.0 (10.0-16.0), 20.0 (16.0-23.0) minutes. Two (6.9%) minor and 5 (17.2%) major (Clavien-Dindo≥III) postoperative complications occurred. At 2 years of follow-up, patient and transplant survival was 100% (n=29) and 93.1% (n=27). After the 14th RAKT, the rewarming time (P=0.01) and venous anastomosis duration (P=0.004) were statistically shorter. CONCLUSION: Living-donor robotic-assisted kidney transplantation, performed by a surgeon skilled robotic surgery, ensures good functional results in the medium term. LEVEL OF EVIDENCE: 3.

[Renal cell carcinoma in candidates for renal transplantation and recipients of a kidney transplant: The French guidelines from CTAFU]. / Recommandations françaises du Comité de transplantation de l'association française d'urologie (CTAFU) : carcinome rénal sur reins natifs chez le patient transplanté rénal ou en attente de transplantation.

OBJECTIVE: To define guidelines for the management of renal cell carcinoma of the native kidney (NKRCC) in kidney transplant (KTx) recipients and renal cell carcinoma (RCC) in end-stage renal disease (ESRD) patients candidates for renal transplantation. METHOD: A review of the literature following a systematic approach (Medline) was conducted by the CTAFU to report renal cell carcinoma epidemiology, screening, diagnosis and management in KTx candidates and recipients. References were assessed according to a predefined process to propose recommendations with the corresponding levels of evidence. RESULTS: ESRD patients are at higher risk of RCC with a standardized incidence ratio of approximately 4,5 as compared with general population. NKRCC tumors occur in 1 to 3 % of KTx recipients with a 10 to 15-fold increased risk as compared with general population, especially in patients with acquired multicystic kidney disease. Most authors suggest yearly monitoring of the native kidneys using ultrasound imaging. Radical nephrectomy (either open or laparoscopic approach) is the preferred treatment of NKRCC in KTx recipients and RCC in ESRD. Surveillance in a valid option in small or cystic renal masses. In the localized setting, change in immunosuppressive therapy is not recommended besides perioperative avoidance of mTOR inhibitor to limit morbidity. CTAFU does not recommend a mandatory waiting time after nephrectomy for RCC in ESRD patients candidates for renal tranplantation when tumor stage

[Living donor nephrectomy: The French guidelines from CTAFU]. / Recommandations françaises du Comité de transplantation de l'Association française d'urologie (CTAFU) : néphrectomie pour don de rein.

OBJECTIVE: To propose surgical recommendations for living donor nephrectomy. METHOD: Following a systematic approach, a review of the literature (Medline) was conducted by the CTAFU regarding functional and anatomical assessment of kidney donors, including which side the kidney should be harvested from. Distinct surgical techniques and approaches were evaluated. References were considered with a predefined process to propose recommendations with the corresponding levels of evidence. RESULTS: The recommendations clarify the legal and regulatory framework for kidney donation in France. A rigorous assessment of the donor is one of the essential prerequisites for donor safety. The impact of nephrectomy on kidney function needs to be anticipated. In case of modal vascularization of both kidneys without a relative difference in function or urologic abnormality, removal of the left kidney is the preferred choice to favor a longer vein. Mini-invasive approaches for nephrectomy provide faster donor recovery, less donor pain and shorter hospital stay than open surgery. CONCLUSION: These French recommendations must contribute to improving surgical management of candidates for kidney donation.

Prostate cancer before renal transplantation: A multicentre study.

INTRODUCTION: The surgical issues of renal transplantation (RT) after localized prostate cancer (PC) treatment and oncological outcomes after transplantation in patients on the waiting list with a history of PC were unknown. We conducted a retrospective multicentre study including all patients with PC diagnosed before the kidney transplantation. METHODS: Fifty-two patients were included from December 1993 to December 2015. The median age at diagnosis of PC was 59.8years old. RESULTS: The median PSA rate at diagnosis was 7ng/mL. Twenty-seven, Twenty-four, and one PC were respectively low, intermediate and high risk according to d'Amico classification. Forty-three patients were treated by radical prostatectomy (RP): 28 retropubic, 15 laparoscopic and 3 by a perineal approach. Eighteen patients had a lymph node dissection. Four patients were treated with external radiotherapy and 2 by brachytherapy. Eight patients underwent radiotherapy after surgery. The median time between PC treatment and RT was 35.7 months. The median operating time for the renal transplantation was 180min (IQR 150-190; min 90-max 310) with a median intraoperative bleeding of 200mL (IQR 100-290; min 50-max 2000). A history of lymphadenectomy did not significantly lengthen operative time (P=0.34). No recurrence of PC was observed after a median follow of 36months. CONCLUSION: PC discovered before RT should be treated with RP to assess the risk of recurrence and decrease waiting for a RT. If the PC is at low risk of recurrence, it seems possible to shorten the waiting time before the RT after a multidisciplinary discussion meeting. LEVEL OF EVIDENCE: 4.

[Polycystic kidney disease and kidney transplantation]. / Prise en charge de la polykystose rénale autosomique dominante avant transplantation rénale.

OBJECTIVES: To perform a state of the art about autosomal dominant polykystic kidney disease (ADPKD), management of its urological complications and end stage renal disease treatment modalities. MATERIAL AND METHODS: An exhaustive systematic review of the scientific literature was performed in the Medline database (http://www.ncbi.nlm.nih.gov) and Embase (http://www.embase.com) using different associations of the following keywords (MESH): "autosomal dominant polykystic kidney disease", "complications", "native nephrectomy", "kidney transplantation". Publications obtained were selected based on methodology, language, date of publication (last 10 years) and relevance. Prospective and retrospective studies, in English or French, review articles; meta-analysis and guidelines were selected and analyzed. This search found 3779 articles. After reading titles and abstracts, 52 were included in the text, based on their relevance. RESULTS: ADPKD is the most inherited renal disease, leading to end stage renal disease requiring dialysis or renal transplantation in about 50% of the patients. Many urological complications (gross hematuria, cysts infection, renal pain, lithiasis) of ADPKD required urological management. The pretransplant evaluation will ask the challenging question of native nephrectomy only in case of recurrent kidney complications or large kidney not allowing graft implantation. The optimum timing for native nephrectomy will depend on many factors (dialysis or preemptive transplantation, complication severity, anuria, easy access to transplantation, potential living donor). CONCLUSION: Pretransplant management of ADPKD is challenging. A conservative strategy should be promoted to avoid anuria (and its metabolic complications) and to preserve a functioning low urinary tract and quality of life. When native nephrectomy should be performed, surgery remains the gold standard but renal arterial embolization may be a safe option due to its low morbidity.

De novo kidney graft tumors: results from a multicentric retrospective national study.

De novo tumors in renal allografts are rare and their prevalence is underestimated. We therefore analyzed renal cell carcinomas arising in renal allografts through a retrospective French renal transplant cohort. We performed a retrospective, multicentric survey by sending questionnaires to all French kidney transplantation centers. All graft tumors diagnosed after transplantation were considered as de novo tumors. Thirty-two centers participated in this study. Seventy-nine tumors were identified among 41 806 recipients (Incidence 0.19%). Patients were 54 men and 25 women with a mean age of 47 years old at the time of diagnosis. Mean tumor size was 27.8 mm. Seventy-four (93.6%), 53 (67%) and 44 tumors (55.6%) were organ confined (T1-2), low grade (G1-2) and papillary carcinomas, respectively. Four patients died of renal cell carcinomas (5%). The mean time lapse between transplantation and RCC diagnosis was 131.7 months. Thirty-five patients underwent conservative surgery by partial nephrectomy (n = 35, 44.3%) or radiofrequency (n = 5; 6.3%). The estimated 5 years cancer specific survival rate was 94%. Most of these tumors were small and incidental. Most tumors were papillary carcinoma, low stage and low grade carcinomas. Conservative treatment has been preferred each time it was feasible in order to avoid a return to dialysis.

[Kidney transplantation in obese recipients: review of the Transplantation Committee of the French Association of Urology]. / Transplantation rénale et receveurs obèses : revue du comité de transplantation de l'Association française d'urologie.

INTRODUCTION: Transplantation Committee of the French Association of Urology (CTAFU) conducted a review of the complication of kidney transplantation in obese recipients. MATERIAL AND METHODS: A bibliographic research in French and English using Medline with the keywords "obesity", "body mass index", "kidney transplantation", "graft function", "survival", "wound complications", "graft rejection" and "graft survival" was performed. We limited the review for the last fifteen years because of the change in immunosuppressive treatment area. Only studies with more than 20 obese patients were selected. RESULTS: Wound or infectious postoperative complications and delayed graft function are more frequent in obese patients than in non-obese recipients. Similarly, transplant survival at 5 years is lower in obese patients. On the other hand, patient survival and acute rejection are the same between the two groups if recipient selection is carefully made, particularly with regard to heart complication. CONCLUSION: Kidney transplantation in obese patients is not an easy surgery with known complication. Obese patients will take time before transplantation to explain all the risk and a regular heart follow-up is crucial if we don't want to reduce patient survival. But obese survival is better if we proceed to kidney transplantation than if they stay on dialysis, arguing for a non-exclusion of the waiting list. So there is the need for a national study concerning obese patients on waiting list to enact future guidelines.

[Should we consider a complementary treatment after a renal colic drained by an ureteral stent?]. / Faut-il envisager un traitement complémentaire après une colique néphrétique drainée par une sonde JJ ?

PURPOSE: The aim of the study was to evaluate if only ureteral stent removing after complicated renal colic (RC) could prevent from complementary treatment (shock-wawe lithortripsy or ureteroscopy). PATIENTS AND METHODS: Data from 95 patients, 39 women and 56 men, who had an ureteral stent for complicated RC from 2005 to 2010 were retrospectively collected. Mean age was 46.4 ± 17.2 years. After the initial management, another hospitalization was organized where patients had ureteral stent removing under local anesthesia, then an abdominal CT-scan without injection and complementary treatment of ureteral stones (none or ESWL or ureteroscopy). Parameters studied were age, sex, stone size, location of calcul. Quantitative values were compared with Student's t test. Qualitative values were compared with the Chi(2). P<0.05 was considered statistically significant. RESULTS: Mean duration between the two hospitalizations were 1.58 ± 1.84 months. Sixty-one patients (64.2%) had no more urolithiasis. In these patients, mean size of urolithiasis was 5.85 ± 2.33 mm. Location of urolithiasis in distal, mild and proximal ureter was 77%, 3% and 20% respectively. Thirty-four patients (35.8%) had persistant lithiasis after CT-scan. Location of stone in distal, mild and proximal ureter was 17.5%, 5.8% and 76.7% respectively. CONCLUSION: After management of complicated renal colic by ureteral stent, 64% of patients had spontaneous elimination of stones after removing of ureteral stent, especially in women and pelvic ureter.

Duodenal villous atrophy: a cause of chronic diarrhea after solid-organ transplantation.

Persistent diarrhea is commonly observed after solid organ transplantation (SOT). A few cases of mycophenolate mofetil (MMF)-induced duodenal villous atrophy (DVA) have been previously reported in kidney-transplant patients with chronic diarrhea. Herein, we report on the incidence and characteristics of DVA in SOT patients with chronic diarrhea. One hundred thirty-two SOT patients with chronic diarrhea underwent an oesophago-gastroduodenoscopy (OGD) and a duodenal biopsy after classical causes of diarrhea have been ruled out. DVA was diagnosed in 21 patients (15.9%). It was attributed to mycophenolic acid (MPA) therapy in 18 patients (85.7%) (MMF [n = 14] and enteric-coated mycophenolate sodium [n = 4]). MPA withdrawal or dose reduction resulted in diarrhea cessation. The incidence of DVA was significantly higher in patients with chronic diarrhea receiving MPA compared to those who did not (24.6% vs. 5.1%, p = 0.003). DVA was attributed to a Giardia lamblia parasitic infection in two patients (9.5%) and the remaining case was attributed to azathioprine. In these three patients, diarrhea ceased after metronidazole therapy or azathioprine dose reduction. In conclusion, DVA is a frequent cause of chronic diarrhea in SOT recipients. MPA therapy is the most frequent cause of DVA. An OGD should be proposed to all transplant recipients who present with persistent diarrhea.

[Laparoscopic radical cystectomy in elderly patients with bladder cancer: feasibility and evaluation of morbidity]. / Cystectomie radicale coelioscopique pour cancer de vessie, chez les sujets de plus de 70ans : faisabilité et étude de la morbidité

OBJECTIVES: To evaluate the feasibility and morbidity and mortality of laparoscopic radical cystectomy for bladder cancer in elderly patients. METHODS: Prospective study conducted between January 2003 and May 2009 in 22 patients, one woman and 21 men, who underwent laparoscopic radical cystectomy for bladder cancer. Mean patient age was 76.2+/-4.3 years. The median preoperative ASA score was 2 (1-3). The indication for surgery was an invasive muscle bladder tumour in 18 cases and noninvasive muscle bladder cancer refractory to conservative treatment (chemotherapy, immunotherapy) in four cases. Ileal conduit was carried out in 15 cases. An ileal neobladder was fashioned in six cases using Camey's technique. One bilateral cutaneous ureterostomy was performed. RESULTS: There was one conversion to open surgery. One intraoperative complication was noted (left obturator nerve injury). Mean blood loss was 377.5+/-341.2ml. No perioperative death was observed. Mean time to resumption of oral fluids was 2.4+/-1.6 days and mean time to resumption of solids was 4.5+/-1.6 days. Mean time to resumption of bowel movements was 3.9+/-1.9 days. Mean critical care unit was 4.2+/-1.4 days. Five patients (22.7 %) had postoperative complications. Postoperative narcotic analgesics were necessary in 60 % of cases. Mean hospital stay was 11.0+/-3.0 days. Mean patient follow-up was 46.4+/-20.8 months. CONCLUSIONS: Laparoscopic radical cystectomy for bladder cancer in elderly patients is associated with low morbidity, and a limited hospital stay.

[Long-term outcome of patients with renal transplant and neural tube defect]. / Suivi au long terme des patients transplantés rénaux ayant un dysraphisme spinal.

PURPOSE: To evaluate the long term outcome of renal transplant in patients with a neural tube defect causing voiding dysfunctions. PATIENT AND METHODS: Between 1993 and 2010, 18 cadaveric renal transplants were performed in 16 patients (5 females and 11 males) older than 15 years with a neural tube defect and voiding dysfunction. RESULTS: The patients had dialysis since the mean age of 27.4 and have been transplanted at the mean age of 32.2. The survival rate of the first kidney transplant was 93.75% at 1 year and 63.3% at 5 and 10 years respectively. With a mean follow-up of 6.67 years, 11 out of 16 first transplants remained functional (68.75%) The median survival of the first transplants was 13.52 years. At the end of the follow-up, 13 out of 18 transplants were still functional (72.2%). The mean serum creatinine level was 123.9 micromol/l with a mean glomerular filtration rate estimated by the simplified MDRD formula of 67 ml/min for the 13 still functional transplants. Before transplantation, 66% of patients had a neuro-urologic assessment versus 100% thereafter. CONCLUSION: Renal transplantation in patients with neural tube defect is feasible without surgical particularities to those of other renal failure causes. These type of patients represented less than 1% of the followed cohort with an average graft survival rate of 63.3% at five and 10 years. The median survival time of the first graft was 13.52 years.

[Domino transplantation of a living-donor kidney graft affected by thrombotic microangiopathy: surgical aspects]. / Transplantation domino à partir d'un donneur vivant d'un rein greffé atteint d'une micro-angiopathie thrombotique: aspects chirurgicaux.

We report surgical aspects of the first case of retransplantation of a kidney initially retrieved from a cadaveric donor, then on a first recipient which developed a recurrent severe and intractable thrombotic microangiopathy on the allograft.

[Assessment in a urological department of nurses' workload for neurological patients]. / Evaluation de la charge en soins paramédicaux des patients neurologiques dans un service d'urologie.

OBJECTIVES: To assess the nurses' workload in care of the neurological patients operated in a department of urology and compare it to the nurses' workload of oncological patients. METHOD: Between 2006 and 2007, a prospective study was realized in 15 consecutive patients with neurogenic voiding dysfunction managed by laparoscopic cystectomy and ileal conduit urinary diversion. The nurses' workload was assessed by the soins infirmiers individualisés à la personne soignée (SIIPS) indicator. Three types of care were so estimated: basic care, technical care and relational care. Results were compared with the first 15 patients in whom, during the same period, a laparoscopic cystectomy and ileal conduit urinary diversion was performed to treat a bladder cancer. RESULTS: The nurses' workload in basic care was higher for the neurological patient's compared to the oncological patients the day before the intervention and from the third postoperative day until the 8th postoperative day. The nurses' workload in relational care was higher in the neurological patient's the 2nd, 3rd, 6th and 7th postoperative days. No difference was noted in terms of technical care between both groups. CONCLUSION: Except the operative day and the first postoperative day, the nurses' workload in relational and basic care is higher in the neurological patient's than in the oncological patients. No difference was noted in terms of technical care between both groups.

[Prospective study of the clinical and urodynamic results of intradetrusor botulinum toxin injections for the treatment of neurogenic overactive bladder]. / Etude prospective des résultats cliniques et urodynamiques des injections intradétrusoriennes de toxine botulique dans le traitement de l'hyperactivité détrusorienne neurogène.

OBJECTIVE: To evaluate the clinical and urodynamic efficacy and duration of efficacy of intradetrusor botulinum toxin A (BTA) injections in patients with neurogenic overactive bladder refractory to anticholinergic therapy. PATIENTS AND METHODS: Between 2004 and 2005, 33 patients (19 men and 14 women), with neurogenic overactive bladder were treated by intradetrusor injections of 300 U of BTA (Botox) in 30 points. All patients were refractory to, intolerant of or presented contraindications to anticholinergic therapy. All patients voided by intermittent self-catheterization. RESULTS: Six weeks after BTA injections, the success rate was 75.8%, with improvement in 12.1% of cases and failure in 9.1% of cases. The mean number of self-catheterizations per 24 h was significantly decreased (6.37 versus 5.2, P=0.02), the maximum voiding volume was increased (321.68 ml versus 536.25 ml, P=0.002), the mean number of episodes of incontinence per 24 h was decreased (7.39 versus 0.03, P<0.0001), the proportion of patients with incontinence was decreased (66.66% versus 6.04%, P<0.0001), the mean maximum cystomanometric capacity was increased (286.75 ml versus 554.16 ml, P=0.002) and the mean maximum intravesical pressure was decreased (54.8 cm H(2)O versus 5.3 cm H(2)O, P<0.0001). After BTA injections, 87.8 % of patients no longer experienced uninhibited contractions. The median duration of clinical efficacy was 7.03 months. At 12 months, injections were still effective clinically in 21.2 % of patients. CONCLUSION: Intradetrusor BTA injections are an effective and well tolerated treatment for neurogenic overactive bladder. Their clinical efficacy persisted for more than 12 months in more than 20% of cases.

Prognostic value of a combination of IPSS, flow rate and residual urine volume compared to pressure-flow studies in the preoperative evaluation of symptomatic BPH.

OBJECTIVE: Evaluate the predictive value of a combination of IPSS, uroflowmetry and ultrasound determination of residual urine volume in the determination of bladder outflow obstruction (BOO) and in predicting treatment outcome. METHODS: Forty-five out of a group of 60 BPH symptomatic patients were included. Preoperative evaluation: urine culture, PSA, uroflowmetry with sonographic measurement of post-void residual urine, DRE, IPSS with quality of life questions and pressure-flow study. Selection criteria for surgery were IPSS > 16 and Qmax < 10 ml/s. Transurethral resection of the prostate was performed in these patients; the control visit was performed at 3 months. Treatment success was defined as Qmax above 15 ml/s, residual urine of less than 100 ml, a 50% reduction in IPSS and absence of urinary retention. RESULTS: Urodynamic abnormalities were found in 42 patients (93.3%): 19 had detrusor instability, 5 patients showed impaired contractility, 37 patients had proven BOO, and 8 patients were unobstructed or mildly obstructed. The overall success rate was 86% when measured by the IPSS. Its preoperative value was 16.9, and dropped significantly to 4 (P = 0.005). The score improved significantly after surgery only in the obstructed group compared to the non-obstructed group (P = 0.001), however preoperative IPSS did not correlate with objective treatment results. CONCLUSIONS: A high proportion of patients successfully operated (71.1%) had a combination of IPSS > 16 and Qmax < 10 ml/s, although BOO could not be accurately predicted with non-invasive methods alone. Patients with no or mild infravesical obstruction had only minimal improvement of IPSS and uroflowmetry following surgery.

Chemoattractants MDC and TARC are secreted by malignant B-cell precursors following CD40 ligation and support the migration of leukemia-specific T cells.

The use of tumor cells as vaccines in cancer immunotherapy is critically dependent on their capacity to initiate and amplify tumor-specific immunity. Optimal responses may require the modification of the tumor cells not only to increase their immunogenicity but also to improve their ability to recruit effector cells to the tumor sites or sites of tumor antigen exposure. It has been reported that CD40 cross-linking of acute lymphoblastic leukemia (ALL) cells significantly increases their immunogenicity and allows the generation and expansion of autologous antileukemia cytotoxic T lymphocytes. This study demonstrates that the CD40 ligation of these tumor cells also induces the secretion of the CC-chemokines MDC and TARC. Supernatants from malignant cells cultured in the presence of sCD40L promote the migration of activated T cells that express CCR4, the common specific receptor for MDC and TARC. More importantly, the supernatants from CD40-stimulated tumor cells also support the transendothelial migration of autologous CCR4(+) antileukemia T cells. Therefore, the results demonstrate that the delivery to leukemia cells of a single physiologic signal, that is, CD40 cross-linking, simultaneously improves tumor cell immunogenicity and induces potent chemoattraction for T cells. (Blood. 2001;98:533-540)

Expression and immunogenicity of oncofetal antigen-immature laminin receptor in human renal cell carcinoma.

PURPOSE: The 32 to 44 kDa. oncofetal antigen-immature laminin receptor (OFA-iLR) is a multifunctional protein expressed by various tumors, including breast, lung, ovary and prostate carcinoma as well as lymphoma. OFA-iLR has been implicated in tumor invasiveness, metastasis and growth. Interferon-gamma producing effector T cells and interleukin (IL)-10 producing suppressor T cells specific for OFA-iLR have been described. MATERIALS AND METHODS: The 43515 IgG2a anti-OFA-iLR monoclonal antibody was used to detect OFA-iLR expression in human renal cell carcinoma tissue by flow cytometry and immunoblotting. Spontaneous or therapy induced immune responses against OFA-iLR were determined in patients with metastatic renal cell carcinoma. Proliferative and cytokine (interferon-gamma and IL-10) responses of peripheral blood mononuclear cells from patients with renal cell carcinoma against recombinant OFA-iLR were assessed. RESULTS: Using flow cytometry OFA-iLR was detected in all 13 tumors tested. Immunoblotting revealed differences in OFA-iLR expression in renal cell carcinoma and normal kidney tissue. OFA-iLR specific proliferative and cytokine responses of mononuclear cells were detected in all 6 patients tested. Importantly evidence was also obtained that treating metastatic renal cell carcinoma with tumor lysate pulsed dendritic cells would enhance OFA-iLR specific immunity. CONCLUSIONS: This study demonstrates that OFA-iLR is an immunogenic tumor associated antigen in human renal cell carcinoma. OFA-iLR specific effector T cells producing interferon-gamma may have a role in the control of tumor growth, whereas suppressor T cells producing IL-10 may promote tumor tolerance and, thus, tumor progression.