Prognostic Value of Tumor-Infiltrating Lymphocytes in Resected Pancreatic Ductal Adenocarcinoma: A Single-Center Retrospective Australian Study

TL;DR

This study finds that high levels of immune cells in pancreatic cancer tumors are linked to better survival after surgery.

Contribution

The study is the first to assess tumor-infiltrating lymphocytes in Australian pancreatic cancer patients using standardized H&E methods.

Findings

High stromal TIL density was associated with improved overall survival and disease-free survival.

A higher lymph node ratio was linked to worse survival outcomes.

TIL assessment using H&E sections is feasible and may have prognostic value.

Abstract

Introduction

Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, even after curative-intent resection. Tumor-infiltrating lymphocytes (TILs) assessed by immunohistochemistry have prognostic value, but standardized assessment on routine H&E sections is not established, particularly in Australian cohorts. This pilot study evaluated stromal TIL density in resected PDAC on H&E sections using the International Immuno-Oncology Biomarker Working Group (ITWG) guidelines and explored its association with survival and key clinicopathological metrics.

Methods

We conducted a retrospective cohort study of 21 consecutive patients who underwent curative-intent resection for histologically confirmed PDAC at an Australian tertiary center between September 2016 and January 2025. Stromal TIL density was quantified on H&E sections and categorized a priori as low (<15%) or high (≥15%) lymphocytic infiltration of the tumor stroma. Overall survival (OS) and disease-free survival (DFS) were analyzed using Kaplan-Meier methods and log-rank tests. Univariable Cox regression was performed, followed by an exploratory multivariable Cox model incorporating stromal TIL category, lymph node ratio (LNR), and vascular invasion.

Results

Median follow-up was 17 months (range, 3-99), with 11 deaths (52%) and 12 recurrences (57%). Using the prespecified threshold of 15% stromal TIL density, 10 patients had low stromal TILs, and 11 had high stromal TILs. Compared with low TILs, high TILs were associated with improved OS (median not reached vs. 16 months; log-rank p = 0.029) and DFS (median not reached vs. nine months; log-rank p = 0.026). In the exploratory multivariable model, high TILs remained associated with improved OS (HR 0.15, p = 0.033) and DFS (HR 0.18, p = 0.024). A higher LNR was associated with poorer OS (HR 3.42 per 10% increase, p = 0.005) and DFS (HR 2.41 per 10% increase, p = 0.010). When analyzed as a continuous variable (per 5% increase), stromal TIL density showed a consistent direction of effect without statistical significance for OS (HR 0.94, p = 0.155) or DFS (HR 0.94, p = 0.115).

Conclusions

In this single-center Australian pilot cohort, high stromal TIL density assessed on routine H&E sections was associated with improved OS and DFS following PDAC resection. These findings support the feasibility and potential prognostic utility of stromal TIL assessment using ITWG guidelines and warrant validation in larger multicenter studies.

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