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Updated: Jun 12, 2026
Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells
Published on: February 8, 2018
Soluble CD27 differentially predicts resistance to anti-PD1 alone but not with anti-CTLA-4 in melanoma
Ikuan Sam1,2, Nadine Benhamouda1,2, Lucie Biard3
1Universite Paris Cite, INSERM, PARCC, Paris, France.
Abstract:
Metastatic melanoma can be treated with anti-PD-1 monotherapy or in combination with anti-CTLA-4 or anti-Lag3. However, combination therapy is associated with a high risk of toxicity. Recently, we reported that high plasma soluble CD27 (sCD27) levels reflect the intratumoral interaction of CD70-CD27 and dysfunctional T cells in the tumor microenvironment of renal cell carcinoma. In this study, we first characterized the intratumoral expression of CD70 and CD27 in melanoma tumors and their interaction in vivo. We then reported a significant association between baseline sCD27 and anti-PD-1 resistance as assessed by progression-free survival, overall survival, or 12-month complete response in two prospective cohorts of melanoma patients. Multivariate analysis confirmed that sCD27 was independently associated with clinical outcomes. Notably, sCD27 did not predict clinical response to combination therapy in either cohort. This differential predictive value of sCD27 for the two therapeutic options was later confirmed by propensity score analysis. Our results suggest that high plasma sCD27 levels predict poorer efficacy of anti-PD1 monotherapy in metastatic melanoma, justifying therapeutic escalation with a combination of anti-PD1 and anti-CTLA-4.
Insights
High soluble CD27 (sCD27) levels in melanoma patients predict poor response to anti-PD-1 therapy. This finding supports using combination treatments for better outcomes in metastatic melanoma.
Area of Science:
- Immunology
- Oncology
- Biomarkers
Background:
- Metastatic melanoma treatment involves anti-PD-1 monotherapy or combination therapies (e.g., anti-CTLA-4, anti-Lag3).
- Combination therapies offer higher efficacy but increased toxicity.
- Soluble CD27 (sCD27) is a potential biomarker linked to T-cell dysfunction in the tumor microenvironment.
Purpose of the Study:
- To investigate the role of CD70 and CD27 expression and interaction within melanoma tumors.
- To determine if baseline plasma soluble CD27 (sCD27) levels can predict treatment response in metastatic melanoma patients.
- To assess the differential predictive value of sCD27 for anti-PD-1 monotherapy versus combination therapy.
Main Methods:
- Characterization of intratumoral CD70 and CD27 expression and interaction in melanoma.
- Analysis of baseline sCD27 levels in two prospective cohorts of metastatic melanoma patients.
- Multivariate and propensity score analyses to evaluate the association of sCD27 with clinical outcomes and treatment response.
Main Results:
- High baseline plasma sCD27 levels were significantly associated with resistance to anti-PD-1 monotherapy.
- sCD27 independently predicted progression-free survival, overall survival, and 12-month complete response.
- sCD27 did not predict clinical response to combination therapy (anti-PD-1 plus anti-CTLA-4).
Conclusions:
- Elevated plasma sCD27 levels are a negative predictive biomarker for anti-PD-1 monotherapy in metastatic melanoma.
- These findings suggest that high sCD27 may warrant therapeutic escalation with combination therapy (anti-PD-1 and anti-CTLA-4).
- sCD27 shows differential predictive value for anti-PD-1 monotherapy compared to combination regimens.
