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Prognostic and predictive significance of GITR in metastatic renal cell carcinoma
O Y Balçık1, D Akın, G S Ceylan
1Medical Oncology, Mardin Training and Research Hospital, Mardin, Turkey.
Objective:
Renal cell carcinoma (RCC) has gradually increased in recent years. There have been significant developments in metastatic RCC in recent years with the introduction of immune control point inhibitors. Glucocorticoid-induced tumor necrosis factor (TNF) receptor-related protein (GITR) is a co-stimulatory molecule and is seen in the highest amounts in activated CD4+ T lymphocytes and CD8+ T lymphocytes, forkhead box protein 3 (FOXP3) positive regulatory T cells (Treg). GITR leads to an increase in interleukin (IL)-2 and CD25 and Interferon Gamma. It shows an anti-tumoural effect by inhibiting the suppressive functions of FOXP3+ regulatory cells (Treg). Therefore, we aimed to evaluate the prognostic and predictive effect of GITR, tumor-infiltrating lymphocytes (CD4+CD8) (TIL), and FOXP3 in patients with metastatic RCC.
Patients And Methods:
Patients diagnosed with pathologically confirmed metastatic renal cancer between 2016 and 2021 were included in our study. Clinicopathological features and some laboratory tests were recorded. GITR, CD4, CD8, and FOXP3 were evaluated by immunohistochemistry (IHC) from biopsies or nephrectomy material and recorded.
Results:
The study included 41 patients. The median progression-free survival (PFS) was 10.5 months, and the median overall survival (OS) was 13.9 months. Median PFS was 7.9 months for the GITR-low group and 18.9 months for the GITR-high group. Median PFS was statistically significant and longer for the GITR-high group than the GITR-low group (p=0.003). When patients who received nivolumab in the 2nd line were evaluated, median PFS was found to be 5.7 months in the GITR-low group and 15.7 months in the GITR-high group. Median PFS was statistically significantly higher in the GITR-high group than in the GITR-low group (p=0.026).
Conclusions:
In patients with metastatic RCC, higher GITR was associated with better PFS. At the same time, in patients using nivolumab, better PFS was seen in the GITR high group. If supported by prospective studies, GITR can be used as both a prognostic and predictive marker.
Insights
Higher Glucocorticoid-induced TNF receptor (GITR) levels in metastatic renal cell carcinoma (RCC) patients correlate with improved progression-free survival (PFS). This suggests GITR may serve as a prognostic and predictive marker, particularly for patients treated with nivolumab.
Area of Science:
- Immunology
- Oncology
- Biomarker Discovery
Background:
- Metastatic renal cell carcinoma (RCC) incidence is rising, with immune checkpoint inhibitors offering new therapeutic avenues.
- Glucocorticoid-induced tumor necrosis factor receptor (GITR) is a co-stimulatory molecule on T cells and regulatory T cells (Tregs), influencing anti-tumor immunity.
- GITR's role in inhibiting suppressive Treg functions suggests potential as an anti-cancer therapeutic target.
Purpose of the Study:
- To investigate the prognostic and predictive value of GITR, tumor-infiltrating lymphocytes (TILs: CD4+CD8), and FOXP3 in metastatic RCC patients.
- To assess the association between GITR expression and patient outcomes, including progression-free survival (PFS) and overall survival (OS).
- To determine if GITR expression predicts response to nivolumab treatment in metastatic RCC.
Main Methods:
- Retrospective analysis of 41 patients with pathologically confirmed metastatic RCC diagnosed between 2016 and 2021.
- Immunohistochemistry (IHC) was used to evaluate GITR, CD4, CD8, and FOXP3 expression in tumor biopsies or nephrectomy specimens.
- Clinicopathological data and laboratory test results were collected and analyzed.
Main Results:
- Median PFS was 10.5 months and median OS was 13.9 months for the entire cohort.
- Patients with high GITR expression had significantly longer median PFS (18.9 months) compared to those with low GITR expression (7.9 months) (p=0.003).
- In patients treated with nivolumab, high GITR expression was associated with significantly improved median PFS (15.7 months) versus low GITR (5.7 months) (p=0.026).
Conclusions:
- Elevated GITR expression in metastatic RCC is linked to better PFS.
- High GITR expression appears to predict a favorable response to nivolumab therapy in metastatic RCC.
- GITR holds promise as a prognostic and predictive biomarker for metastatic RCC, warranting further validation in prospective studies.
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