Absence of Bcl-2 and Fas/CD95/APO-1 predicts the response to immunotherapy in metastatic renal cell carcinoma

R Maruyama1, K Yamana, T Itoi

  • 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.

British Journal of Cancer
|October 13, 2006
PubMed

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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