Table 5_Role of CD28+ PD-1+ Tc cells in immune response and prognosis prediction in hepatocellular carcinoma.docx
Background<p>CD28<sup>+</sup>PD-1<sup>+</sup> Tc cells (CD8<sup>+</sup> T cells) constitute a dysfunctional subset of T cell; however, the mechanisms underlying their dysfunction and their significance in hepatocellular carcinoma (HCC) remain unclear. We aim...
محفوظ في:
| المؤلف الرئيسي: | |
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| مؤلفون آخرون: | , , , , , , |
| منشور في: |
2025
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| الموضوعات: | |
| الوسوم: |
إضافة وسم
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| الملخص: | Background<p>CD28<sup>+</sup>PD-1<sup>+</sup> Tc cells (CD8<sup>+</sup> T cells) constitute a dysfunctional subset of T cell; however, the mechanisms underlying their dysfunction and their significance in hepatocellular carcinoma (HCC) remain unclear. We aimed to elucidate the prognostic significance and molecular characteristics of CD28<sup>+</sup>PD-1<sup>+</sup> Tc cell infiltration in HCC.</p>Methods<p>We established a single-cell HCC transcriptional map, focusing on cell-cell communication and trajectory analysis of CD28<sup>+</sup>PD-1<sup>+</sup> Tc cells. We assessed the correlation between CD28<sup>+</sup>PD-1<sup>+</sup> Tc-cell enrichment and prognosis and investigated potential molecular mechanisms using enrichment analyses. Flow cytometry was used to compare CD28<sup>+</sup>PD-1<sup>+</sup> Tc-cell infiltration between HCC and adjacent normal tissues and cytotoxic factors and immune checkpoint expression were evaluated.</p>Results<p>Overall, 25,644 T cells were identified from single-cell RNA sequencing data from 10 HCC samples and corresponding normal samples. Overall T-cell infiltration was lower in HCC tissues, with significantly higher CD28<sup>+</sup>PD-1<sup>+</sup> Tc-cell infiltration. Bulk RNA sequencing data integration revealed a correlation between higher CD28<sup>+</sup>PD-1<sup>+</sup> Tc-cell infiltration and significantly worse prognosis. Flow cytometry confirmed higher CD28<sup>+</sup>PD-1<sup>+</sup> Tc-cell enrichment in HCC tissues. Additionally, cytotoxic factor expression was significantly lower in CD28<sup>+</sup>PD-1<sup>+</sup> Tc cells than in CD28<sup>-</sup>PD-1<sup>+</sup> Tc cells, with lower expression of TIGIT and TIM-3 immune checkpoint molecules.</p>Conclusions<p>Significantly high CD28<sup>+</sup>PD-1<sup>+</sup> Tc-cell enrichment in HCC indicates potential immune dysfunction. CD28<sup>+</sup>PD-1<sup>+</sup> Tc-cell enrichment may serve as a sensitive prognostic marker and indicator for predicting treatment responses.</p> |
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