Sarcomatoid and rhabdoid (S/R) renal cell carcinoma (RCC) are highly aggressive tumors with limited molecular and clinical characterization. Emerging evidence suggests immune checkpoint inhibitors (ICI) are particularly effective for these tumors, although the biological basis for this property is largely unknown. Here, we evaluate multiple clinical trial and real-world cohorts of S/R RCC to characterize their molecular features, clinical outcomes, and immunologic characteristics. We find that S/R RCC tumors harbor distinctive molecular features that may account for their aggressive behavior, including BAP1 mutations, CDKN2A deletions, and increased expression of MYC transcriptional programs. We show that these tumors are highly responsive to ICI and that they exhibit an immune-inflamed phenotype characterized by immune activation, increased cytotoxic immune infiltration, upregulation of antigen presentation machinery genes, and PD-L1 expression. Our findings build on prior work and shed light on the molecular drivers of aggressivity and responsiveness to ICI of S/R RCC.

PURPOSE:We sought to validate levels of CD8 + tumor-infiltrating cells (TIC) expressing PD-1 but not TIM-3 and LAG-3 (IF biomarker) (Pignon et al, 2019) and to investigate human endogenous retroviruses (hERVs) as predictors of response to anti-PD-1 in a randomized trial of nivolumab (nivo) versus everolimus (evero) in patients with metastatic clear cell renal cell carcinoma (mccRCC) (CheckMate-025).

Purpose. Assessment of deep myometrial invasion (MI) and lymphovascular space invasion (LVSI) is of utmost importance in preoperative staging of endometrial cancer (EC). Imaging parameters derived respectively from MRI and PET have shown good predictive value. Aim of the present study is to assess the diagnostic performance of hybrid 18F-FDG PET/MRI in EC staging, with particular focus on MI and LVSI detection.Methods. Prospective monocentric study including 35 patients with biopsy-proven EC undergoing preoperative 18F-FDG PET/MRI for staging purpose. Histological examination was the reference standard. PET (SUVmax, SUVmean40, MTV40, TLG40) and MRI (volume index-VI, total tumor volume-TTV, tumor volume ratio-TVR, ADCmean, ADCmin) parameters were calculated on the primary tumor, and their role in predicting histological ndings (grade, high-vs. low-risk groups, LVSI, MI, p53 hyperexpression) was assessed through a ROC analysis.Results. 18F-FDG-PET/MRI identi ed the primary tumor in all patients. In the LVSI detection, PET/MRI demonstrated high accuracy, speci city and negative predictive value (sensitivity=0.8571, speci city=0.9286, accuracy=0.9143, NPV=0.9630, PPV=0.7500). Assessment of MI using PET/MRI correctly staged 27 patients, showing a good positive predictive value (77.1%; sensitivity= 0.7273, speci city=0.8462, accuracy=0.7714, PPV=0.8889, NPV=0.647). VI, TTV, and TVR signi cantly predicted risk groups (p=0.0059, 0.0235, 0.0181, respectively). VI, TTV, TVR, MTV40 and TLG40 signi cantly predicted LVSI (p=0.0023, 0.0068, 0.0068, 0.0027, 0.0139, respectively). Imaging was not able to predict grading, MI nor p53 hyper-expression.Conclusion. 18F-FDG-PET/MRI has good accuracy in preoperative staging of EC; PET and MRI parameters have synergic role in preoperatively predicting LVSI, with MRI parameters being also predictive for EC risk groups.