Introduction <p>Tumour antigen-specific CD8<sup>+</sup>CD39<sup>+</sup> T cells (TSTs) are crucial components of anti-tumour adaptive immunity, which in tumour microenvironment (TME) may be found at various differentiation stages, from early stem-like states to terminal stages of exhaustion. Our aim was the evaluation of TSTs quantitative and qualitative characteristics in hepatocellular carcinoma (HCC) TME, depending on whether they exhibit stem-like or exhaustion features.</p> Methods <p>We analyzed 100 HCC patients undergoing curative hepatectomy. Multiplex immunohistochemistry (CD8/CD39/TCF1, CD8/CD39/TOX) was applied on tissue microarray sections with digital imaging used to evaluate T cell infiltration in tumour center, periphery and adjacent non-neoplastic liver. Tertiary lymphoid structures (TLS) were assessed on H&amp;E-stained slides.</p> Results <p>In HCC TME, 72% of CD8<sup>+</sup> T cells co-express CD39, while 44% of CD8<sup>+</sup>CD39<sup>+</sup> TSTs co-express TCF1 (stem-like) and over 50% co-express TOX (exhausted). High CD8<sup>+</sup>CD39<sup>+</sup> T cell density in tumour periphery was linked to longer overall survival (<i>p</i> = 0.016). Increased CD8<sup>+</sup>CD39<sup>-</sup>TCF1<sup>+</sup> T cell infiltration in tumour center and periphery correlated with worse prognosis (<i>p</i> = 0.009). TLS presence was associated with high TST density (<i>p</i> &lt; 0.001).</p> Conclusions <p>Patients with HCC and high CD8<sup>+</sup>CD39<sup>+</sup> TSTs density exhibiting a tumour-reactive phenotype have improved survival, suggesting the potential role of CD8/CD39 immunohistochemistry as a prognostic tool for personalised therapeutic strategies.</p>

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Antigen-specific CD8+CD39+ cytotoxic T cell density in the microenvironment of hepatocellular carcinoma predicts patient survival

  • Konstantina Dimopoulou,
  • Aris Spathis,
  • Christina Papamichail,
  • Aikaterini Athanasiadou,
  • Abraham Pouliakis,
  • Christakis Risilia,
  • Despoina Myoteri,
  • Panayiotis Kokoropoulos,
  • Manousos Konstantoulakis,
  • Ioannis G. Panayiotides,
  • Nikolaos Arkadopoulos,
  • Dina Tiniakos,
  • Periklis G. Foukas

摘要

Introduction

Tumour antigen-specific CD8+CD39+ T cells (TSTs) are crucial components of anti-tumour adaptive immunity, which in tumour microenvironment (TME) may be found at various differentiation stages, from early stem-like states to terminal stages of exhaustion. Our aim was the evaluation of TSTs quantitative and qualitative characteristics in hepatocellular carcinoma (HCC) TME, depending on whether they exhibit stem-like or exhaustion features.

Methods

We analyzed 100 HCC patients undergoing curative hepatectomy. Multiplex immunohistochemistry (CD8/CD39/TCF1, CD8/CD39/TOX) was applied on tissue microarray sections with digital imaging used to evaluate T cell infiltration in tumour center, periphery and adjacent non-neoplastic liver. Tertiary lymphoid structures (TLS) were assessed on H&E-stained slides.

Results

In HCC TME, 72% of CD8+ T cells co-express CD39, while 44% of CD8+CD39+ TSTs co-express TCF1 (stem-like) and over 50% co-express TOX (exhausted). High CD8+CD39+ T cell density in tumour periphery was linked to longer overall survival (p = 0.016). Increased CD8+CD39-TCF1+ T cell infiltration in tumour center and periphery correlated with worse prognosis (p = 0.009). TLS presence was associated with high TST density (p < 0.001).

Conclusions

Patients with HCC and high CD8+CD39+ TSTs density exhibiting a tumour-reactive phenotype have improved survival, suggesting the potential role of CD8/CD39 immunohistochemistry as a prognostic tool for personalised therapeutic strategies.