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Updated: Jul 11, 2025
Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells
Published on: February 8, 2018
Comprehensive analyses of immune tumor microenvironment in papillary renal cell carcinoma
Manon de Vries-Brilland1, Nathalie Rioux-Leclercq2, Maxime Meylan3
1Department of Medical Oncology, Integrated Centers of Oncology (ICO) Paul Papin, Angers, France.
Background:
Papillary renal cell carcinoma (pRCC) is the most common non-clear cell RCC, and associated with poor outcomes in the metastatic setting. In this study, we aimed to comprehensively evaluate the immune tumor microenvironment (TME), largely unknown, of patients with metastatic pRCC and identify potential therapeutic targets.
Methods:
We performed quantitative gene expression analysis of TME using Microenvironment Cell Populations-counter (MCP-counter) methodology, on two independent cohorts of localized pRCC (n=271 and n=98). We then characterized the TME, using immunohistochemistry (n=38) and RNA-sequencing (RNA-seq) (n=30) on metastatic pRCC from the prospective AXIPAP trial cohort.
Results:
Unsupervised clustering identified two "TME subtypes", in each of the cohorts: the "immune-enriched" and the "immune-low". Within AXIPAP trial cohort, the "immune-enriched" cluster was significantly associated with a worse prognosis according to the median overall survival to 8 months (95% CI, 6 to 29) versus 37 months (95% CI, 20 to NA, p=0.001). The two immune signatures, Teff and JAVELIN Renal 101 Immuno signature, predictive of response to immune checkpoint inhibitors (CPI) in clear cell RCC, were significantly higher in the "immune-enriched" group (adjusted p<0.05). Finally, five differentially overexpressed genes were identified, corresponding mainly to B lymphocyte populations.
Conclusion:
For the first time, using RNA-seq and immunohistochemistry, we have highlighted a specific immune TME subtype of metastatic pRCC, significantly more infiltrated with T and B immune population. This "immune-enriched" group appears to have a worse prognosis and could have a potential predictive value for response to immunotherapy, justifying the confirmation of these results in a cohort of metastatic pRCC treated with CPI and in combination with targeted therapies.
Trial Registration Number:
NCT02489695.
Insights
Papillary renal cell carcinoma (pRCC) has a poorly understood immune microenvironment. This study identified an "immune-enriched" subtype associated with worse prognosis and potential immunotherapy response in metastatic pRCC.
Area of Science:
- Oncology
- Immunology
- Genomics
Background:
- Papillary renal cell carcinoma (pRCC) is the most common non-clear cell renal cancer.
- Metastatic pRCC is associated with poor patient outcomes.
- The immune tumor microenvironment (TME) in pRCC is largely uncharacterized.
Purpose of the Study:
- To comprehensively evaluate the immune TME in metastatic pRCC.
- To identify potential therapeutic targets within the pRCC TME.
- To characterize immune cell infiltration and gene expression in pRCC.
Main Methods:
- Quantitative gene expression analysis of TME using Microenvironment Cell Populations-counter (MCP-counter) on two localized pRCC cohorts.
- Immunohistochemistry and RNA-sequencing on metastatic pRCC samples from the AXIPAP trial.
- Unsupervised clustering to identify distinct TME subtypes.
Main Results:
- Two TME subtypes were identified: "immune-enriched" and "immune-low".
- The "immune-enriched" subtype in metastatic pRCC showed significantly worse overall survival (8 vs. 37 months).
- Immune signatures predictive of response to immune checkpoint inhibitors (CPI) were higher in the "immune-enriched" group.
Conclusions:
- A specific "immune-enriched" TME subtype, rich in T and B immune cells, was identified in metastatic pRCC.
- This subtype is associated with a worse prognosis and may predict response to immunotherapy.
- Further validation in CPI-treated metastatic pRCC cohorts is warranted.
