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Updated: Jul 19, 2026

A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies
Published on: April 12, 2017
Absence of Bcl-2 and Fas/CD95/APO-1 predicts the response to immunotherapy in metastatic renal cell carcinoma
1Division of Molecular Oncology, Department of Signal Transduction Research, Graduate School of Medical and Dental Sciences, Niigata University, Asahimachi 1-757, Niigata 951-8510, Japan.
Abstract:
Immunotherapy is the only available treatment for metastatic renal cell cancer (RCC), but the response rate is only about 20% and the treatment is occasionally associated with severe adverse effects. Thus, the selection of patients with a high susceptibility to immunotherapy is needed; however, there is no promising molecular marker that can predict the response to immunotherapy for RCC. This study was carried out to elucidate the potential role of apoptosis-related molecules Bcl-2 and Fas, as well as apoptotic and proliferating indexes (AI, PI) as predictors of the susceptibility of metastatic RCC to immunotherapy. Immunohistochemical examination of tumour tissues from 40 patients with metastatic RCC undergoing postoperative immunotherapy after radical nephrectomy was performed. Patients with progressive disease (PD) after immunotherapy presented with decreased survival (P=0.006). Progressive disease correlated with higher PI in the primary lesion (P=0.0087). All primary tumours of CR or PR patients were negative for Bcl-2, whereas among NC+PD patients, 40.6% were positive for Bcl-2 (P=0.0373). Patients in whom the primary tumours were both Bcl-2- and Fas-negative showed significantly better responses to immunotherapy in comparison with the remaining group (P=0.0022). The Bcl-2 and Fas status of the primary lesion may become useful criteria for the selection of patients with metastatic RCC for immunotherapy.
Insights
Predicting immunotherapy response in metastatic renal cell cancer (RCC) is crucial. Bcl-2 and Fas protein expression in primary tumors may help select patients likely to benefit from immunotherapy, improving treatment outcomes.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Immunotherapy is the sole treatment for metastatic renal cell cancer (RCC), but its efficacy is limited, with only a 20% response rate.
- Severe adverse effects can occur with immunotherapy, necessitating patient selection strategies.
- Currently, no reliable molecular markers exist to predict immunotherapy response in RCC patients.
Purpose of the Study:
- To investigate the potential of apoptosis-related molecules Bcl-2 and Fas, along with apoptotic and proliferating indexes (AI, PI), as predictors of immunotherapy response in metastatic RCC.
- To identify biomarkers that can aid in selecting patients with a higher susceptibility to immunotherapy for metastatic RCC.
Main Methods:
- Immunohistochemical analysis was performed on tumor tissues from 40 patients with metastatic RCC who received postoperative immunotherapy.
- Assessment of Bcl-2 and Fas protein expression, as well as apoptotic and proliferating indexes (AI, PI) in primary tumors.
- Correlation of these markers with treatment response (Complete Response, Partial Response, No Change, Progressive Disease) and patient survival.
Main Results:
- Patients experiencing progressive disease (PD) post-immunotherapy had significantly decreased survival.
- Higher proliferating index (PI) in primary tumors correlated with progressive disease.
- Absence of Bcl-2 in primary tumors was associated with better treatment response (CR or PR).
- Primary tumors negative for both Bcl-2 and Fas demonstrated significantly better immunotherapy response compared to other groups.
Conclusions:
- Bcl-2 and Fas protein expression in primary renal cell carcinoma lesions may serve as valuable predictive markers for immunotherapy response.
- These markers could aid in selecting metastatic RCC patients who are more likely to benefit from immunotherapy, potentially improving treatment outcomes and reducing unnecessary adverse effects.
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