The behaviour of clear cell renal cell carcinoma (CCRCC) is highly unpredictable. Despite adequate initial surgery, 20 to 30 % of patients will develop local recurrence or metastasis during follow-up. Usual clinical and pathology parameters tend to classify most patients in an intermediate prognosis group, and molecular markers to determine prognosis more accurately are needed. A key feature of CCRCC is its abundant vascularization. Factors that upregulate angiogenesis, such as hypoxia and the presence of immune cells including macrophages, also modulate tumour proliferation and metastasis. We studied angiogenesis, as defined by nestin-positive capillaries, and tumour infiltration by macrophages especially in the good prognosis pT1 subgroup of CCRCC. We assessed whether these parameters are associated with metastatic extension and survival in CCRCC. The expression of HIF1α, CAIX, nestin, CD68 and CD163 was assessed by immunohistochemistry on a tissue microarray (TMA) containing tissue samples from 257 consecutive patients with sporadic CCRCC. Factors associated with progression-free (PFS) and overall survival (OS) were analysed. The presence of nestin-positive tumour vessels was independently associated with shorter PFS in the whole cohort and in the pT1 subgroup. The presence of tumour-infiltrating macrophages was independently associated with shorter OS in the whole cohort and in the pT1 subgroup. The presence of nestin-positive endothelial cells is associated with early relapse, especially in the pT1 subgroup and may help to select patients for antiangiogenic treatment. The presence of tumour-infiltrating M2-type macrophages is a strong predictor of short survival and may be used to adapt treatment strategy.

Chronic allograft dysfunction (CAD), defined as the replacement of functional renal tissue by extracellular matrix proteins, remains the first cause of graft loss. The aim of our study was to explore the potential role of the cannabinoid receptor 1 (CB1) during CAD. We retrospectively quantified CB1 expression and correlated it with renal fibrosis in 26 kidney‐transplanted patients who underwent serial routine kidney biopsies. Whereas CB1 expression was low in normal kidney grafts, it was highly expressed during CAD, especially in tubular cells. CB1 expression significantly increased early on after transplantation, from day 0 (D0) to month 3 post‐transplant (M3) (22.5% ± 15.4% vs 33.4% ± 13.8%, P < .01), and it remained stable thereafter. CB1 expression correlated with renal fibrosis at M3 (P = .04). In an in vitro model of tacrolimus‐mediated fibrogenesis by tubular cells, we found that tacrolimus treatment significantly induced mRNA and protein expression of CB1 concomitantly to col3a1 and col4a3 up regulation. Administration of rimonabant, a CB1 antagonist, blunted collagen synthesis by tubular cells (P < .05). Overall, our study strongly suggests an involvement of the cannabinoid system in the progression of fibrosis during CAD and indicates the therapeutic potential of CB1 antagonists in this pathology.