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Updated: Jun 17, 2025
Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells
Published on: February 8, 2018
TIGIT expression in renal cell carcinoma infiltrating T cells is variable and inversely correlated with PD-1 and LAG3
Oscar Perales1, Lucia Jilaveanu2, Adebowale Adeniran3
1Yale School of Medicine, New Haven, CT, USA.
Purpose:
Immune checkpoint inhibitors have revolutionized the treatment of renal cell carcinoma (RCC), but many patients do not respond to therapy and the majority develop resistant disease over time. Thus, there is increasing need for alternative immunomodulating agents. The co-inhibitory molecule T-cell immunoglobulin and ITIM domain (TIGIT) may play a role in resistance to approved immune checkpoint inhibitors and is being investigated as a potential therapeutic target. The purpose of this study was to quantify TIGIT positivity in tumor-infiltrating T cells in RCC.
Methods:
We employed tissue microarrays containing specimens from primary RCC tumors, adjacent normal renal tissue, and RCC metastases to quantify TIGIT within tumor-infiltrating CD3+ T cells using quantitative immunofluorescent analysis. We also compared these results to TIGIT+ CD3+ levels in four other tumor types (melanoma, non-small cell lung, cervical, and head and neck cancers).
Results:
We did not observe significant differences in TIGIT positivity between primary RCC tumors and patient-matched metastatic samples. We found that the degree of TIGIT positivity in RCC is comparable to that in lung cancer but lower than that in melanoma, cervical, and head and neck cancers. Correlation analysis comparing TIGIT positivity to previously published, patient-matched spatial proteomic data by our group revealed a negative association between TIGIT and the checkpoint proteins PD-1 and LAG3.
Conclusion:
Our findings support careful evaluation of TIGIT expression on T cells in primary or metastatic RCC specimens for patients who may be treated with TIGIT-targeting antibodies, as increased TIGIT positivity might be associated with a greater likelihood of response to therapy.
Insights
This study quantified T-cell immunoglobulin and ITIM domain (TIGIT) in renal cell carcinoma (RCC) tumors. Higher TIGIT expression in RCC may indicate a better response to TIGIT-targeting immunotherapies.
Area of Science:
- Immunology
- Oncology
- Translational Research
Background:
- Immune checkpoint inhibitors (ICIs) have transformed renal cell carcinoma (RCC) treatment.
- Many RCC patients exhibit resistance or develop resistance to current ICIs.
- The co-inhibitory molecule T-cell immunoglobulin and ITIM domain (TIGIT) is a potential therapeutic target for overcoming resistance.
Purpose of the Study:
- To quantify TIGIT expression in tumor-infiltrating T cells within RCC.
- To compare TIGIT positivity in RCC with other cancer types.
- To explore the relationship between TIGIT and other immune checkpoint proteins in RCC.
Main Methods:
- Quantitative immunofluorescent analysis of TIGIT in tumor-infiltrating CD3+ T cells.
- Tissue microarrays of primary RCC, normal renal tissue, and metastatic RCC specimens.
- Comparison of TIGIT+ CD3+ levels across RCC and four other cancer types (melanoma, non-small cell lung, cervical, head and neck).
Main Results:
- No significant difference in TIGIT positivity between primary and metastatic RCC.
- RCC TIGIT positivity is comparable to lung cancer, lower than melanoma, cervical, and head and neck cancers.
- A negative association was observed between TIGIT and PD-1/LAG3 checkpoint proteins in RCC.
Conclusions:
- TIGIT expression in RCC T cells warrants evaluation for patients considering TIGIT-targeting therapies.
- Increased TIGIT positivity may correlate with a higher likelihood of therapeutic response.
- Findings support TIGIT as a potential biomarker and therapeutic target in RCC.
