BackgroundTumor-infiltrating immune cells have been linked to prognosis and response to immunotherapy; however, the levels of distinct immune cell subsets and the signals that draw them into a tumor, such as the expression of antigen presenting machinery genes, remain poorly characterized. Here, we employ a gene expression-based computational method to profile the infiltration levels of 24 immune cell populations in 19 cancer types.ResultsWe compare cancer types using an immune infiltration score and a T cell infiltration score and find that clear cell renal cell carcinoma (ccRCC) is among the highest for both scores. Using immune infiltration profiles as well as transcriptomic and proteomic datasets, we characterize three groups of ccRCC tumors: T cell enriched, heterogeneously infiltrated, and non-infiltrated. We observe that the immunogenicity of ccRCC tumors cannot be explained by mutation load or neo-antigen load, but is highly correlated with MHC class I antigen presenting machinery expression (APM). We explore the prognostic value of distinct T cell subsets and show in two cohorts that Th17 cells and CD8+ T/Treg ratio are associated with improved survival, whereas Th2 cells and Tregs are associated with negative outcomes. Investigation of the association of immune infiltration patterns with the subclonal architecture of tumors shows that both APM and T cell levels are negatively associated with subclone number.ConclusionsOur analysis sheds light on the immune infiltration patterns of 19 human cancers and unravels mRNA signatures with prognostic utility and immunotherapeutic biomarker potential in ccRCC.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-016-1092-z) contains supplementary material, which is available to authorized users.

The NCCN Guidelines for Kidney Cancer provide multidisciplinary recommendations for the clinical management of patients with clear cell and non–clear cell renal cell carcinoma, and are intended to assist with clinical decision-making. These NCCN Guidelines Insights summarize the NCCN Kidney Cancer Panel discussions for the 2020 update to the guidelines regarding initial management and first-line systemic therapy options for patients with advanced clear cell renal cell carcinoma.

Background Counseling patients with enhancing renal mass currently occurs in the context of significant uncertainty regarding tumor pathology. Objective We evaluated whether radiographic features of renal masses could predict tumor pathology and developed a comprehensive nomogram to quantitate the likelihood of malignancy and high-grade pathology based on these features. Design, setting, and participants We retrospectively queried Fox Chase Cancer Center’s prospectively maintained database for consecutive renal masses where a Nephrometry score was available. Intervention All patients in the cohort underwent either partial or radical nephrectomy. Measurements The individual components of Nephrometry were compared with histology and grade of resected tumors. We used multiple logistic regression to develop nomograms predicting the malignancy of tumors and likelihood of high-grade disease among malignant tumors. Results and limitations Nephrometry score was available for 525 of 1750 renal masses. Nephrometry score correlated with both tumor grade (p < 0.0001) and histology (p < 0.0001), such that small endophytic nonhilar tumors were more likely to represent benign pathology. Conversely, large interpolar and hilar tumors more often represented high-grade cancers. The resulting nomogram from these data offers a useful tool for the preoperative prediction of tumor histology (area under the curve [AUC]: 0.76) and grade (AUC: 0.73). The model was subjected to out-of-sample cross-validation; however, lack of external validation is a limitation of the study. Conclusions The current study is the first to objectify the relationship between tumor anatomy and pathology. Using the Nephrometry score, we developed a tool to quantitate the preoperative likelihood of malignant and high-grade pathology of an enhancing renal mass.

The NCCN Guidelines for Kidney Cancer provide multidisciplinary recommendations for diagnostic workup, staging, and treatment of patients with renal cell carcinoma (RCC). These NCCN Guidelines Insights focus on recent updates to the guidelines, including changes to certain systemic therapy recommendations for patients with relapsed or stage IV RCC. They also discuss the addition of a new section to the guidelines that identifies and describes the most common hereditary RCC syndromes and provides recommendations for genetic testing, surveillance, and/or treatment options for patients who are suspected or confirmed to have one of these syndromes.

The NCCN Guidelines for Kidney Cancer focus on the screening, diagnosis, staging, treatment, and management of renal cell carcinoma (RCC). Patients with relapsed or stage IV RCC typically undergo surgery and/or receive systemic therapy. Tumor histology and risk stratification of patients is important in therapy selection. The NCCN Guidelines for Kidney Cancer stratify treatment recommendations by histology; recommendations for first-line treatment of ccRCC are also stratified by risk group. To further guide management of advanced RCC, the NCCN Kidney Cancer Panel has categorized all systemic kidney cancer therapy regimens as “Preferred,” “Other Recommended Regimens,” or “Useful in Certain Circumstances.” This categorization provides guidance on treatment selection by considering the efficacy, safety, evidence, and other factors that play a role in treatment selection. These factors include pre-existing comorbidities, nature of the disease, and in some cases consideration of access to agents. This article summarizes surgical and systemic therapy recommendations for patients with relapsed or stage IV RCC.

Objectives The treatment of localized renal cell carcinoma remains overly subjective. The R.E.N.A.L.- Nephrometry Score (NS) quantifies the salient characteristics of renal mass anatomy in an objective and reproducible manner. We evaluated treatment patterns of solid renal masses based on quantifiable anatomic features using Nephrometry. Methods Nephrometry scores were available in 615 patients in our prospective kidney tumor database (2000-2010). The NS sum and its individual component scores were analyzed to determine their relationship to treatment approach. Results Median age, age-adjusted Charlson Co-Morbidity Index (CCI), and estimated GFR were 60 years (25-89), 2 (0-10), and 80.5 ml/min (5.1-120.0), respectively. Increasing tumor complexity as measured by a higher overall Nephrometry Score was associated with both radical nephrectomy (RN) and open partial nephrectomy (PN) (p<0.0001). Compared to patients who underwent PN, patients treated with RN had significantly higher size (R), central proximity (N), and location (L) component scores (p<0.001). Furthermore, tumors treated with a RN were more often hilar (p<0.001). Similarly, compared to minimally-invasive PN (laparoscopic or robotic), open PN was associated with an increasing individual component score for size, endophycity and central proximity to the collecting system (p<0.001) and non-polar location (p=0.016). Conclusions The R.E.N.A.L. – Nephrometry score standardizes reporting of solid renal masses and appears to effectively stratify by treatment type. Although only one part of the treatment decision-making process, Nephrometry aids in objectifying previously subjective measures.

Objectives-Nephron-sparing surgery is an established treatment for patients with small renal masses. The laparoscopic approach has emerged as an alternative to open nephron-sparing surgery, but it is recognized to be technically challenging. The robotic surgical system may enable faster and greater technical proficiency, facilitating a minimally invasive approach to more difficult lesions while reducing ischemia time. We report experience with 100 robot assisted partial nephrectomy (RAPN) operations performed at our institution.Methods-100 RAPN operations were performed for suspicious solid renal lesions over 21 months. Clinicopathologic variables, nephrometry scores, operative parameters, and renal functional outcomes were prospectively recorded and analyzed.Results-Median tumor size was 2.8 cm (range 1.0 to 8). Nephrometry scores of resected lesions were low in 47.9% of patients, medium in 45.7%, and high in 6.4% patients. 46.8% of patients had tumors > 50% intraparenchymal, and 61.7% had tumors <7mm from the renal sinus or collecting system. 17.0% were touching a first order vessel in the renal hilum. Mean warm ischemia time was 25.5 minutes (range 0 to 53). Mean change in postoperative GFR improved 6.32 ml/min/1.73m 2 (range −41.9 to 68.9). Histology was renal cell carcinoma in 81% (87/107) of tumors. There were 5 microscopically positive margins on final pathology (5.7%). Major and minor complication rates were 6% and 5%, respectively. There were 2 conversions to open surgery.Conclusions-RAPN appears to be a safe and technically feasible minimally invasive approach to nephron-sparing surgery even in more complex cases, with acceptable pathologic and renal function outcomes.

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