Proliferative potential and response to nivolumab in clear cell renal cell carcinoma patients.

Background: Biomarkers predicting immunotherapy response in metastatic renal cell cancer (mRCC) are lacking. PD-L1 immunohistochemistry is a complementary diagnostic for immune checkpoint inhibitors (ICIs) in mRCC, but has shown minimal clinical utility and is not used in routine clinical practice. Methods: Tumor specimens from 56 patients with mRCC who received nivolumab were evaluated for PD-L1, cell proliferation (targeted RNA-seq), and outcome. Results: For 56 patients treated with nivolumab as a standard of care, there were 2 complete responses and 8 partial responses for a response rate of 17.9%. Dividing cell proliferation into tertiles, derived from the mean expression of 10 proliferation-associated genes in a reference set of tumors, poorly proliferative tumors (62.5%) were more common than moderately (30.4%) or highly proliferative (8.9%) counterparts. Moderately proliferative tumors were enriched for PD-L1 positive (41.2%), compared to poorly proliferative counterparts (11.4%). Objective response for moderately proliferative (29.4%) tumors was higher than that of poorly (11.4%) proliferative counterparts, but not statistically significant (p = .11). When cell proliferation and negative PD-L1 tumor proportion scores were combined statistically significant results were achieved (p = .048), showing that patients with poorly proliferative and PD-L1 negative tumors have a very low response rate (6.5%) compared to moderately proliferative PD-L1 negative tumors (30%). Conclusions: Cell proliferation has value in predicting response to nivolumab in clear cell mRCC patients, especially when combined with PD-L1 expression. Further studies which include the addition of progression-free survival (PFS) along with sufficiently powered subgroups are required to further support these findings.

Incidental findings on chest computed tomography are common and linked to inflammation in HIV-infected adults.

BACKGROUND: Chest imaging is performed for a variety of reasons in HIV-infected adults. There are limited data on the prevalence of incidental findings, progression of these findings over time and the relationship with inflammation in antiretroviral therapy (ART)-treated HIV-infected adults. METHODS: This study utilized data from a randomized clinical trial of rosuvastatin in HIV-infected adults on ART. Incidental findings were reported from chest computed tomography (CT) scans obtained for coronary artery calcium score at entry, week 48 and 96. Markers of immune activation and inflammation were measured concurrently. Poisson regression and generalized estimating equations were used. RESULTS: A total of 147 participants were enrolled. Median age was 46 years, 78% were male, 68% African American and 63% current smokers. At baseline, 57% of participants had at least one incidental lung finding (ILF) and four additional participants had at least one ILF by week 96. At baseline, older age, current smoking, lower nadir CD4+ T-cell count and low-density lipoprotein and higher lipoprotein-associated phospholipase A2 (Lp-PLA2) were independently associated with having a greater number of ILFs. In the longitudinal analyses, older age, lower nadir CD4+ T-cell count and higher baseline soluble tumour necrosis factor α-receptor I (sTNF-RI) were independently associated with having a greater number of ILFs over 96 weeks. CONCLUSIONS: Over half of participants had at least one incidental finding on chest CT. Beyond traditional factors of older age and smoking, lower nadir CD4+ T-cell count and higher markers of inflammation were associated with having a greater number of ILFs in HIV-infected adults on ART.