PTX3 modulates the immunoflogosis in tumor microenvironment and is a prognostic factor for patients with clear cell renal cell carcinoma

Abstract Background: Several models and markers were developed and found to predict outcome of advanced renal cell carcinoma. This study aimed to evaluate the prognostic value of the ratio of maximum to minimum tumor diameter (ROD) in metastatic clear cell renal cell carcinoma (mccRCC).Methods: Patients with mccRCC (n=213) treated with sunitinib from January 2008 to December 2018 were identified. Cut-off value for ROD was determined using receiver operating characteristic. Patients with different ROD scores were grouped and evaluated. Survival outcomes were estimated by Kaplan-Meier method.Results: The optimal ROD cutoff value of 1.34 was determined for progression free survival (PFS) and overall survival (OS). Patients in ROD≥1.34 group had shorter PFS (9.6 versus 17.7 months, p<0.001) and OS (25.5 versus 32.6 months, p<0.001) than patients in ROD<1.34 group. After adjustment for other factors, multivariate analysis showed ROD≥1.34 was an independent prognostic factor for PFS (p<0.001) and OS (p=0.006). Patients in ROD³1.34 group presented higher proportions of T3/4 stage (92.9% versus 7.1%, p=0.012), WHO/ISUP grade III/IV (72.0% versus 28.0%, p=0.010), tumor necrosis (71.0% versus 29.0%, p=0.039), sarcomatoid differentiation (79.1% versus 20.9%, p=0.007), poor MSKCC risk score (78.4% versus 21.6%, p<0.001) and poor IMDC risk score (74.4% versus 25.6%, p<0.001) than ROD<1.34 group.Conclusion: Primary tumor with higher ROD was an independently prognostic factor for both PFS and OS in patients with mccRCC who received targeted therapy. Higher ROD was also associated with high T stage, high WHO/ISUP grade, sarcomatoid features, tumor necrosis, poor MSKCC and IMDC risk score.

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494: The Chemokine Receptor CXCR3 is an Independent Prognostic Factor for Patients with Localized Clear Cell Renal Cell Carcinoma

The Journal of Urology ◽

10.1016/s0022-5347(18)30734-1 ◽

2007 ◽

Vol 177 (4S) ◽

pp. 165-165

Author(s):

Tobias Klatte ◽

David B. Seligson ◽

John T. Leppert ◽

Nazy Zomorodian ◽

Fairooz F. Kabbinavar ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Prognostic Factor ◽

Cell Carcinoma ◽

Chemokine Receptor ◽

Renal Cell ◽

Clear Cell ◽

Independent Prognostic Factor ◽

Cell Renal Cell Carcinoma

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Relation between clinicopathological findings and PD-1 or PD-L1 status in non-clear cell renal cell carcinoma by a multicenter study.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.7_suppl.654 ◽

2019 ◽

Vol 37 (7_suppl) ◽

pp. 654-654

Author(s):

Hiroaki Matsumoto ◽

Kazuhiro Nagao ◽

Masahiro Samoto ◽

Junichi Mori ◽

Kosuke Shimizu ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Multivariate Analysis ◽

Prognostic Factors ◽

Prognostic Factor ◽

Cell Carcinoma ◽

Multicenter Study ◽

Renal Cell ◽

Clear Cell ◽

Pathological Findings ◽

Cell Renal Cell Carcinoma

654 Background: We investigated correlation of their pathological findings and their prognostic factors in non-clear cell renal cell carcinoma (ncRCC) diagnosed by both regional pathology (RP) and central pathology (CP) in multicenter study. Methods: In January 2005 to December 2014, 140 cases of ncRCC diagnosed by radical or partial nephrectomy were assessed. We assessed their pathological diagnosis by one central pathologist using the 2016 WHO classification tumor of the kidney. We assessed the correlation between clinical parameters or pathological findings and their prognosis. Then, we performed immunohistochemical analysis using PD-1 related antibody in ncRCC. Results: Median follow up was 32.7 months (1-134). Median age was 66 years, 99 males and 41 females. Pathological stage was pT1a: 58, pT1b: 30, pT2a: 17, pT2b: 6, pT3a: 21, pT3b: 2, pT4: 3 cases, respectively. In RP, histology was papillary (PAP): 60 (42.9%), chromophobe (CHR): 49 (35.0%), containing with sarcomatoid components (SAR): 14 (10.0%) and other histology: 17 (12.1%) cases, respectively. The tumors evaluable by CP were 127 cases, PAP: 52 (40.9%), CHR: 31 (24.4%), SAR: 20 (15.7%) and other histology: 24 cases (18.8%), respectively. The overall concordance rate was 59.5% between RP and CP. In multivariate analysis, SAR was extremely poor prognosis in ncRCC. The high neutrophil lymphocyte ratio (NLR) and at high CRP value were also poor prognostic factors. So, we stratified three risk groups using three factors, namely NLR, CRP and SAR. In overall survival, there were significant prognostic differences within three groups (p = 0.0014). In immunohistochemistry, PD-1 or PD-L1 expression correlated with poor overall, cancer specific and recurrence free survival in ncRCC. In multivariate analysis, PD-L1 expression was most significant prognostic factor for ncRCC. Conclusions: These results suggest that Risk stratification by three risk factors is useful prognostic model and the expression of PD-1 and PD-L1 may be a useful prognostic factor in ncRCC.

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Tumor Microenvironment Features as Predictive Biomarkers of Response to Immune Checkpoint Inhibitors (ICI) in Metastatic Clear Cell Renal Cell Carcinoma (mccRCC)

Cancers ◽

10.3390/cancers13020231 ◽

2021 ◽

Vol 13 (2) ◽

pp. 231

Author(s):

Audrey Simonaggio ◽

Nicolas Epaillard ◽

Cédric Pobel ◽

Marco Moreira ◽

Stéphane Oudard ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Tumor Microenvironment ◽

Cell Carcinoma ◽

Renal Cell ◽

Immune Checkpoint Inhibitors ◽

Clear Cell ◽

Checkpoint Inhibitors ◽

Predictive Biomarkers ◽

Cell Renal Cell Carcinoma ◽

Genomic Signatures

Renal cell carcinoma (RCC) is the seventh most frequently diagnosed malignancy with an increasing incidence in developed countries. Despite a greater understanding of the cancer biology, which has led to an increase of therapeutic options, metastatic clear cell renal cell carcinoma (mccRCC) still have a poor prognosis with a median five-years survival rate lower than 10%. The standard of care for mccRCC has changed dramatically over the past decades with the emergence of new treatments: anti-VEGFR tyrosine kinase inhibitors, mTOR Inhibitors and immune checkpoint inhibitors (ICI) such as anti-Programmed cell-Death 1 (PD-1) and anti-anti-Programmed Death Ligand-1 (PD-L1) used as monotherapy or as a combination with anti CTLA-4 or anti angiogenic therapies. In the face of these rising therapeutic options, the question of the therapeutic sequences is crucial. Predictive biomarkers are urgently required to provide a personalized treatment for each patient. Disappointingly, the usual ICI biomarkers, PD-L1 expression and Tumor Mutational Burden, approved in melanoma or non-small cell lung cancer (NSCLC) have failed to distinguish good and poor mccRCC responders to ICI. The tumor microenvironment is known to be involved in ICI response. Innovative technologies can be used to explore the immune contexture of tumors and to find predictive and prognostic biomarkers. Recent comprehensive molecular characterization of RCC has led to the development of robust genomic signatures, which could be used as predictive biomarkers. This review will provide an overview of the components of the RCC tumor microenvironment and discuss their role in disease progression and resistance to ICI. We will then highlight the current and future ICI predictive biomarkers assessed in mccRCC with a major focus on immunohistochemistry markers and genomic signatures.

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