Association between circulating CD39+CD8+ T cells pre-chemoradiotherapy and prognosis in patients with nasopharyngeal carcinoma

Association between circulating CD39+CD8+ T cells pre-chemoradiotherapy and prognosis in patients with nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) remains a significant clinical challenge, particularly due to the risk of distant metastasis, which is a major cause of mortality. Despite advancements in chemoradiotherapy strategies, distant metastasis continues to be a critical issue in the management of NPC. Recent research has highlighted the importance of tumor-specific T cell responses in controlling cancer development, with CD39+ T cells, particularly CD39+CD103+ T cells, being identified as key players in tumor-specific reactivity. This study investigates the predictive value of circulating CD39+CD8+ T cells for metastasis in patients with NPC undergoing chemoradiotherapy.

The study was conducted on 55 patients with newly diagnosed stage III–IVa NPC, who were treated with standard combined chemoradiotherapy. Blood samples were collected from 24 patients before treatment and at 1 month and 6 months post-treatment. Flow cytometry was used to analyze the expression of CD39 and CD103 on T cells, along with markers of T cell exhaustion (PD-1 and Tim-3) and cell differentiation (CD27, CCR7, and CD45RA). The Wilcoxon rank-sum test was employed to compare differences between groups, and Kaplan-Meier analysis was used to assess progression-free survival (PFS).

The results revealed that the expression of circulating CD39+CD8+ and CD39+CD103+CD8+ T cells was significantly higher in patients without distant metastasis compared to those with metastasis. Specifically, the median percentages of CD39+CD8+ T cells were 6.52% in patients without metastasis versus 2.41% in those with metastasis (P=0.038). Similarly, the median percentages of CD39+CD103+CD8+ T cells were 0.72% in patients without metastasis versus 0.26% in those with metastasis (P=0.021). Importantly, most CD39+ T cells did not express PD-1 or Tim-3, indicating that these cells are not exhausted and retain their effector function.

Kaplan-Meier survival analysis demonstrated that patients with high expression of CD39+CD103+CD8+ T cells had significantly better PFS than those with low expression (log-rank value = 4.854, P=0.028). Multivariate Cox regression analysis confirmed that high expression of CD39+CD103+CD8+ T cells was an independent predictor of better PFS (HR, 0.147; 95% CI: 0.028–0.781; P=0.024).

The study also examined the differentiation stages of CD39+CD8+ T cells before treatment. CD39+CD8+ T cells exhibited higher percentages of early, intermediate, and advanced differentiation phenotypes compared to CD39-CD8+ T cells. Specifically, the percentages of early, intermediate, and advanced differentiated CD39+CD8+ T cells were 6.32%, 41.05%, and 27.95%, respectively, while the corresponding percentages for CD39-CD8+ T cells were 2.33%, 21.40%, and 14.95%. In contrast, CD39+CD8+ T cells had significantly lower percentages of naïve and terminally differentiated phenotypes compared to CD39-CD8+ T cells.

Post-treatment analysis showed that the percentage of CD39+CD8+ T cells increased significantly at 1 month post-treatment (10.02% vs. 5.91%, P=0.003) and then decreased at 6 months post-treatment (4.27% vs. 5.91%, P=0.023). The percentage of advanced differentiated CD8+ T cells also increased at 1 month post-treatment (33.10% vs. 21.00%, P=0.031), and the percentage of late differentiated CD8+ T cells increased at both 1 month (23.80% vs. 12.00%, P=0.002) and 6 months post-treatment (28.20% vs. 12.00%, P=0.027). Conversely, the percentage of naïve CD8+ T cells decreased significantly at both 1 month (2.23% vs. 22.00%, P<0.001) and 6 months post-treatment (4.74% vs. 22.00%, P=0.001).

A significant correlation was observed between elevated CD39+CD8+ T cells and increased effector memory T cells at 1 month post-treatment. Specifically, there was a positive correlation between the changes in CD39+CD8+ T cells and intermediate differentiated T cells (r=0.469, P=0.031) and advanced differentiated T cells (r=0.508, P=0.019). This suggests that CD39+CD8+ T cells are stimulated and expanded during treatment, with preserved polyfunctional properties, contributing to the control of metastasis in NPC patients post-chemoradiotherapy.

The study also evaluated the expression of exhaustion markers PD-1 and Tim-3 on CD39+CD8+ T cells. The results showed that most CD39+CD8+ T cells did not express PD-1 or Tim-3, with only 11.46% of CD39+CD8+ T cells expressing PD-1 and 4.77% expressing Tim-3. This indicates that CD39+CD8+ T cells are not exhausted and retain their effector function, which is crucial for their role in controlling metastasis.

In conclusion, this study demonstrates that circulating CD39+CD8+ T cells have preserved effector function and contribute to an improved prognosis and reduced risk of metastasis in NPC patients. The findings suggest that CD39+CD8+ T cells may serve as a useful predictive marker for better prognosis in NPC patients undergoing chemoradiotherapy. The data also highlight the potential of these cells for future adoptive immunotherapy strategies in patients with NPC at high risk of metastasis.

doi.org/10.1097/CM9.0000000000001745

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