PD1-positive tumor-infiltrating lymphocytes are associated with poor clinical outcome after pulmonary metastasectomy for colorectal cancer
Pulmonary metastasectomy (PM) is routinely performed in colorectal cancer (CRC) patients with oligometastatic spreading to the lungs. Patients with an aggressive tumor phenotype should be excluded from PM, since its benefit is outweighed by early tumor recurrence and impaired prognosis. Expression o...
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doaj-77b3934642ed403186d0691cea86e86e2020-11-25T03:24:23ZengTaylor & Francis GroupOncoImmunology2162-402X2017-09-016910.1080/2162402X.2017.13311941331194PD1-positive tumor-infiltrating lymphocytes are associated with poor clinical outcome after pulmonary metastasectomy for colorectal cancerDagmar Kollmann0Thomas Schweiger1Stefan Schwarz2Desislava Ignatova3Yun-Tsan Chang4Gerrit Lewik5Sebastian F. Schoppmann6Wolfram Hoetzenecker7Walter Klepetko8Emmanuella Guenova9Konrad Hoetzenecker10Medical University of ViennaMedical University of ViennaMedical University of ViennaUniversity Hospital Zürich, University of ZurichUniversity Hospital Zürich, University of ZurichMedical University of ViennaMedical University of ViennaUniversity Hospital Zürich, University of ZurichMedical University of ViennaUniversity Hospital Zürich, University of ZurichMedical University of ViennaPulmonary metastasectomy (PM) is routinely performed in colorectal cancer (CRC) patients with oligometastatic spreading to the lungs. Patients with an aggressive tumor phenotype should be excluded from PM, since its benefit is outweighed by early tumor recurrence and impaired prognosis. Expression of PD-1 and its ligands are prognostic factors in a variety of primary tumors. However, their impact on patients' outcome in the setting of PM for CRC has not been evaluated before. 53 CRC patients with pulmonary metastases receiving PM with curative intent were included in this study. Tissue samples of resected pulmonary metastases and available corresponding primary tumors were collected and assessed for PD-1, PD-L1 and PD-L2 expression by tumor-infiltrating lymphocytes (TILs) and tumor cells. Expression patterns were correlated with clinical outcome parameters. PD-1 and PD-L1 expression was commonly found in TILs and tumor cells. Expression levels significantly differed between metastases and primary tumors. High PD-1 expression by TILs was associated with impaired overall survival (low vs high expression (mean, 95% CI): 78 mo (60–96) vs 35 mo (25–44); p = 0.011). Additionally, the subgroup of patients, who experienced an upgrading in their TILs/PD1 status between primary and metastasis had a worse survival outcome compared with patients with the same grade or a downgrading (34 mo (26–42) vs 96 mo (72–120); p = 0.004). Thus, PD-1 expression by TILs is a strong prognostic marker in CRC patients with pulmonary spreading treated by PM. Moreover, this study provides a rationale for a therapeutic PD-1 pathway blockade in the treatment of CRC lung metastases. Future, large-scale studies are warranted to validate the findings of this single-center, retrospective analysis.http://dx.doi.org/10.1080/2162402X.2017.1331194colorectal cancerlung metastasisoutcomepd-1pd-l1prognosispulmonary metastasectomyselection criteria |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Dagmar Kollmann Thomas Schweiger Stefan Schwarz Desislava Ignatova Yun-Tsan Chang Gerrit Lewik Sebastian F. Schoppmann Wolfram Hoetzenecker Walter Klepetko Emmanuella Guenova Konrad Hoetzenecker |
spellingShingle |
Dagmar Kollmann Thomas Schweiger Stefan Schwarz Desislava Ignatova Yun-Tsan Chang Gerrit Lewik Sebastian F. Schoppmann Wolfram Hoetzenecker Walter Klepetko Emmanuella Guenova Konrad Hoetzenecker PD1-positive tumor-infiltrating lymphocytes are associated with poor clinical outcome after pulmonary metastasectomy for colorectal cancer OncoImmunology colorectal cancer lung metastasis outcome pd-1 pd-l1 prognosis pulmonary metastasectomy selection criteria |
author_facet |
Dagmar Kollmann Thomas Schweiger Stefan Schwarz Desislava Ignatova Yun-Tsan Chang Gerrit Lewik Sebastian F. Schoppmann Wolfram Hoetzenecker Walter Klepetko Emmanuella Guenova Konrad Hoetzenecker |
author_sort |
Dagmar Kollmann |
title |
PD1-positive tumor-infiltrating lymphocytes are associated with poor clinical outcome after pulmonary metastasectomy for colorectal cancer |
title_short |
PD1-positive tumor-infiltrating lymphocytes are associated with poor clinical outcome after pulmonary metastasectomy for colorectal cancer |
title_full |
PD1-positive tumor-infiltrating lymphocytes are associated with poor clinical outcome after pulmonary metastasectomy for colorectal cancer |
title_fullStr |
PD1-positive tumor-infiltrating lymphocytes are associated with poor clinical outcome after pulmonary metastasectomy for colorectal cancer |
title_full_unstemmed |
PD1-positive tumor-infiltrating lymphocytes are associated with poor clinical outcome after pulmonary metastasectomy for colorectal cancer |
title_sort |
pd1-positive tumor-infiltrating lymphocytes are associated with poor clinical outcome after pulmonary metastasectomy for colorectal cancer |
publisher |
Taylor & Francis Group |
series |
OncoImmunology |
issn |
2162-402X |
publishDate |
2017-09-01 |
description |
Pulmonary metastasectomy (PM) is routinely performed in colorectal cancer (CRC) patients with oligometastatic spreading to the lungs. Patients with an aggressive tumor phenotype should be excluded from PM, since its benefit is outweighed by early tumor recurrence and impaired prognosis. Expression of PD-1 and its ligands are prognostic factors in a variety of primary tumors. However, their impact on patients' outcome in the setting of PM for CRC has not been evaluated before. 53 CRC patients with pulmonary metastases receiving PM with curative intent were included in this study. Tissue samples of resected pulmonary metastases and available corresponding primary tumors were collected and assessed for PD-1, PD-L1 and PD-L2 expression by tumor-infiltrating lymphocytes (TILs) and tumor cells. Expression patterns were correlated with clinical outcome parameters. PD-1 and PD-L1 expression was commonly found in TILs and tumor cells. Expression levels significantly differed between metastases and primary tumors. High PD-1 expression by TILs was associated with impaired overall survival (low vs high expression (mean, 95% CI): 78 mo (60–96) vs 35 mo (25–44); p = 0.011). Additionally, the subgroup of patients, who experienced an upgrading in their TILs/PD1 status between primary and metastasis had a worse survival outcome compared with patients with the same grade or a downgrading (34 mo (26–42) vs 96 mo (72–120); p = 0.004). Thus, PD-1 expression by TILs is a strong prognostic marker in CRC patients with pulmonary spreading treated by PM. Moreover, this study provides a rationale for a therapeutic PD-1 pathway blockade in the treatment of CRC lung metastases. Future, large-scale studies are warranted to validate the findings of this single-center, retrospective analysis. |
topic |
colorectal cancer lung metastasis outcome pd-1 pd-l1 prognosis pulmonary metastasectomy selection criteria |
url |
http://dx.doi.org/10.1080/2162402X.2017.1331194 |
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