# Association Between Tumor-Infiltrating Immune Cells and Early Recurrence in Ampulla of Vater Carcinoma

## TL;DR

This study finds that early recurrence in a rare type of cancer called Ampulla of Vater carcinoma is linked to aggressive tumor features and specific immune cell activity.

## Contribution

The study identifies immune markers (CD4⁺ T cells, PD-1, PD-L1) associated with early recurrence in Ampulla of Vater carcinoma.

## Key findings

- Early recurrence was linked to higher preoperative CA19-9 levels and aggressive tumor features like vascular and perineural invasion.
- Early recurrence was associated with increased CD4⁺ T cells, PD-1, and PD-L1 expression in tumor tissues.
- Patients with early recurrence had significantly poorer overall survival.

## Abstract

Introduction

Ampulla of Vater carcinoma (AVC) is a rare gastrointestinal malignancy with limited evidence from large-scale clinical studies. Although curative resection remains the standard treatment, early recurrence significantly worsens prognosis. Increasing attention has been paid to the tumor immune microenvironment, particularly immune checkpoint molecules, which influence tumor behavior. This study aimed to identify clinicopathological and immunological factors associated with early recurrence in AVC.

Methods

We retrospectively analyzed 42 patients who underwent curative resection for AVC at Nagasaki University Hospital between October 2005 and March 2022. Early recurrence was defined as tumor relapse within one year after surgery. Immunohistochemical staining was performed for tumor-infiltrating immune cells, including CD4, CD8, PD-1, PD-L1, Foxp3, and TIM3. Statistical analyses included Fisher’s exact test, Mann-Whitney U test, and Kaplan-Meier survival analysis.

Results

Seven patients (16.7%) experienced early recurrence. Compared with the non-early recurrence group, the early-recurrence group had significantly higher preoperative CA19-9 levels (p = 0.009) and higher incidences of vascular invasion (p = 0.002), perineural invasion (p = 0.002), lymph node metastasis, and advanced Union for International Cancer Control (UICC) stage (≥ IIB; both p < 0.05). Immunohistochemically, the early-recurrence group showed significantly increased expression of CD4⁺ T cells, PD-1, and PD-L1 (p < 0.001, 0.004, and < 0.001, respectively), whereas CD8, Foxp3, and TIM3 expression did not differ significantly. Kaplan-Meier analysis demonstrated significantly poorer overall survival in the early-recurrence group (p < 0.001).

Conclusion

Early recurrence of AVC is strongly associated with aggressive pathological features and distinct immune profiles, including increased expression of CD4⁺ T cells, PD-1, and PD-L1. These findings suggest a potential association between the tumor immune microenvironment and early recurrence in AVC. However, the present results should be interpreted as exploratory and hypothesis-generating. Further large-scale studies are warranted to clarify the biological significance of these immune features and their potential therapeutic implications.