Influence of Neoadjuvant Radio-chemotherapy on Tumor-infiltrating Lymphocytes in Squamous Esophageal Cancer

Introduction: Data on influence of radio-chemotherapy (RCT) on tumor-infiltrating lymphocytes (TILs) is scarce and no study addressed this issue in esophageal squamous cell cancer (SCC) so far.

Methods: Tumor specimens of 49 patients with SCC were re-evaluated with immunohistochemical staining with anti-CD3, anti-CD4, anti-CD8, anti-CD25 and anti-FOXP3 antibodies. Lymphocytes were counted in one high power field (0.189 mm(2)) at the periphery and in the centre of tumors.

Results: 21 patients received preoperative RCT, 28 proceeded directly to surgery. There was no significant difference in survival between the two groups (median survival 23.2 months vs. 22.1 months, log rank test p=n.s.). Cox regression analysis showed that no variable had a significant effect on survival. The infiltrating pattern of TILs revealed higher numbers peripherally independent of the administration of RCT. There was a significant decrease in all cell numbers except CD4(+) cells in the centre of the tumors after RCT (CD3(+)p=0.005; CD8(+)p=0.02; CD25(+)p=0.01; FoxP3(+)p=0.01). There were fewer TILs in the periphery after RCT; however, this difference only reached significance in FoxP3(+) cells (p=0.01).

Conclusion: Neoadjuvant RCT reduced the number of TILs in esophageal SCC. This was primarily seen in the centre of tumors and suggests that the effect of RCT on immunological response is located in the centre of tumors.