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Updated: Feb 13, 2026
Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells
Published on: February 8, 2018
[Tim-3: a novel biomarker and therapeutic target in oncology]
Clémence Granier1, Alain Gey2, Charles Dariane3
1Inserm U970, université Paris Descartes Sorbonne Paris-Cité, Paris, France - Équipe labellisée Ligue contre le cancer, Paris, France.
Abstract:
T cells harboring multiple co-inhibitory molecules lose their anti-tumoral functionality. PD-1 is a clinically approved target in cancer therapy, but its expression alone does not mean dysfunctionality. The expression of Tim-3 on numerous cell types (T cell, Treg, dendritic cell, myeloid cells) favors tumor escape to immune cells. Within many tumors, PD-1/Tim-3 coexpressing CD8-T cells lose their ability to secrete cytokines (IFNγ, IL-2, TNFα) and their intratumoral infiltration correlates with a bad prognosis. Tim-3 recently appeared as a potential biomarker of anti-PD-1 resistance. Combined blockade of PD-1 and Tim-3 axis demonstrated potent clinical efficacy in preclinical models and reinforced the rationale of using an anti-Tim-3 to override tumor resistance.
Insights
T cells expressing both PD-1 and Tim-3 are dysfunctional and promote tumor growth. Targeting Tim-3 alongside PD-1 can overcome resistance and restore anti-tumor immunity.
Area of Science:
- Immunology
- Cancer Biology
- T cell Exhaustion
Background:
- Co-inhibitory molecule expression on T cells can lead to loss of anti-tumoral function.
- Programmed Death-1 (PD-1) is a validated cancer immunotherapy target, but its expression alone doesn't equate to T cell dysfunctionality.
- T-cell immunoglobulin and mucin-domain containing-3 (Tim-3) expression on various immune cells facilitates tumor immune evasion.
Purpose of the Study:
- To investigate the role of PD-1 and Tim-3 co-expression on CD8-T cells in tumor immunity.
- To evaluate the therapeutic potential of combined PD-1 and Tim-3 blockade in overcoming anti-PD-1 resistance.
Main Methods:
- Analysis of PD-1 and Tim-3 co-expression on intratumoral CD8-T cells.
- Assessment of cytokine secretion (IFNγ, IL-2, TNFα) by co-expressing T cells.
- Evaluation of combined PD-1 and Tim-3 blockade in preclinical cancer models.
Main Results:
- PD-1/Tim-3 co-expressing CD8-T cells within tumors exhibit impaired cytokine production and correlate with poor prognosis.
- Tim-3 is identified as a potential biomarker for resistance to anti-PD-1 therapy.
- Combined blockade of PD-1 and Tim-3 demonstrated significant efficacy in preclinical settings.
Conclusions:
- Co-expression of PD-1 and Tim-3 on T cells signifies a dysfunctional state contributing to tumor immune escape.
- Targeting the Tim-3 axis is a promising strategy to overcome resistance to PD-1-based immunotherapies.
- Combined PD-1/Tim-3 blockade warrants further investigation for enhanced cancer treatment efficacy.
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