Tumor-infiltrating lymphocyte subsets and tertiary lymphoid structures in pulmonary metastases from colorectal cancer.

Thomas Schweiger,Denise Traxler,Olaf Glueck,Orsolya Rajky,Walter Klepetko,Anna Sophie Berghoff,Konrad Hoetzenecker,Christoph Glogner,Peter Birner,Matthias Preusser

doi:10.1007/s10585-016-9813-y

Thomas Schweiger, Denise Traxler + Show 8 more

Open Access

https://doi.org/10.1007/s10585-016-9813-y

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Abstract

The presence of tumor-infiltrating lymphocytes (TILs) and tertiary lymphoid structures (TLSs) reflects an active inflammatory tumor microenvironment. High density of TILs as well as presence of TLS is associated with improved survival in various solid cancer types. We aimed to describe the density and distribution of TILs and TLS in pulmonary metastases (PMs) from primary colorectal cancer (CRC) and its correlation with clinicopathological variables. Fifty-seven CRC pulmonary metastasectomy specimen (PM) and 31 matched primary CRC specimen were included. Cluster of differentiation (CD)3+, CD8+, CD45RO+ and FoxP3+ TILs were evaluated by immunohistochemistry and density was scored semiquantitatively. TLS were evaluated based on morphological criteria. Survival time was defined from pulmonary metastasectomy to death or last follow up. A marked infiltration with CD3+, CD8+, CD45RO+ and FoxP3+ TILs was evident in CRC PM and matched primary CRC. Further assessment of the immune infiltrate in PM showed that a high density of FOXP3+ TILs at the invasive margin [HR 2.40 (1.11–6.96); P = 0.031] and low density of CD8+ cells in TLS [HR 0.30 (0.14–0.79); P = 0.016] were associated with a worse prognosis in univariate analysis. Moreover, a low CD8/FoxP3-ratio of TILs at the invasive margin (P = 0.042) and in TLS (P = 0.027) conferred an impaired prognosis after pulmonary metastasectomy. Our findings suggest that CRC PM harbor an immune active microenvironment. The balance of CD8+ and FoxP3+ T-cells at the tumor border and in TLS provides prognostic information in patients with CRC PM.Electronic supplementary materialThe online version of this article (doi:10.1007/s10585-016-9813-y) contains supplementary material, which is available to authorized users.

Highlights

Despite advances in the early detection and treatment of colorectal cancer (CRC), the prognosis of patients is impaired as soon as distant metastases occur
The aim of this study was to evaluate the role of tumor-infiltrating lymphocytes (TILs) and tertiary lymphoid structures (TLSs) in pulmonary metastases (PMs) assessing a cohort of patients with CRC lung metastases
CD3? TILs were found in every resected pulmonary metastatic specimen, highlighting the pivotal role of the adaptive immune system in local tumor microenvironment

Summary

Introduction

Despite advances in the early detection and treatment of colorectal cancer (CRC), the prognosis of patients is impaired as soon as distant metastases occur. Synchronous pulmonary spreading is evident in about one out of ten patients with newly diagnosed CRC. An average 5-year cumulative risk of 5.8 % for the development of metachronous pulmonary metastases (PMs) is contributing to the disease burden of patients with CRC [1]. Within the group of patients with CRC lung metastases long-term survival can be achieved by (repeated) pulmonary metastasectomy complemented by chemotherapeutic regimens. The underlying tumor biology is considered to be the main cause for heterogeneity in the outcome of patients with CRC lung metastases. The tumor microenvironment gained increasing attention in the scientific community, especially in groups focusing on metastatic CRC [5,6,7]

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