Heterogeneous tumor‐immune microenvironments between primary and metastatic carcinoid tumors differentially respond to anti‐PD‐L1 antibody therapy
A pulmonary carcinoid tumor is a rare tumor that lacks a validated therapeutic approach for unresectable disease. Understanding the intersite tumor‐immune heterogeneity is essential to harness the immune system for cancer therapy. However, little is known about the tumor‐immune microenvironment (TIM...
Main Authors: | , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Wiley
2021-02-01
|
Series: | Thoracic Cancer |
Subjects: | |
Online Access: | https://doi.org/10.1111/1759-7714.13772 |
id |
doaj-221683a337784d74b60494b237fb4c2f |
---|---|
record_format |
Article |
spelling |
doaj-221683a337784d74b60494b237fb4c2f2021-02-05T06:16:07ZengWileyThoracic Cancer1759-77061759-77142021-02-0112339740110.1111/1759-7714.13772Heterogeneous tumor‐immune microenvironments between primary and metastatic carcinoid tumors differentially respond to anti‐PD‐L1 antibody therapyShinya Sakata0Kosuke Imamura1Yuka Tajima2Yuiko Masuda3Ryo Sato4Chieko Yoshida5Shinichiro Okamoto6Sho Saeki7Yusuke Tomita8Takuro Sakagami9Department of Respiratory Medicine Kumamoto University Hospital Kumamoto JapanDepartment of Respiratory Medicine Kumamoto University Hospital Kumamoto JapanDepartment of Respiratory Medicine Kumamoto University Hospital Kumamoto JapanDepartment of Respiratory Medicine Kumamoto University Hospital Kumamoto JapanLaboratory of Stem Cell and Neuro‐Vascular Biology Genetics and Developmental Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health Bethesda Maryland USADepartment of Respiratory Medicine Kumamoto University Hospital Kumamoto JapanDepartment of Respiratory Medicine Kumamoto University Hospital Kumamoto JapanDepartment of Respiratory Medicine Kumamoto University Hospital Kumamoto JapanDepartment of Respiratory Medicine Kumamoto University Hospital Kumamoto JapanDepartment of Respiratory Medicine Kumamoto University Hospital Kumamoto JapanA pulmonary carcinoid tumor is a rare tumor that lacks a validated therapeutic approach for unresectable disease. Understanding the intersite tumor‐immune heterogeneity is essential to harness the immune system for cancer therapy. However, little is known about the tumor‐immune microenvironment (TIME). Here, we describe a patient who had heterogeneous TIME between primary and metastatic carcinoid tumors which differentially responded to chemoimmunotherapy. A 72‐year‐old man was diagnosed with an advanced pulmonary carcinoid tumor. CT‐guided biopsies of lung and scapular tumors confirmed typical carcinoid (PD‐L1, 1%–24%) and atypical carcinoid tumors (PD‐L1, negative), respectively. Although the primary lung carcinoid tumor showed a partial response, the scapular tumor was significantly enlarged after two cycles of anti‐PD‐L1 antibody therapy in combination with carboplatin plus etoposide. We performed quantitative pathology imaging analysis with fluorescent multiplex immunohistochemistry. CD8+ T cell infiltration was detected in the PD‐L1‐positive primary lung tumor nest; however, it was mostly restrained in the stroma in a PD‐L1‐negative metastatic scapular tumor. Treg infiltrations into both tumor nests and stroma were detected in the lung tumor, which were not detected in the metastatic scapular tumor. This study provides the first evidence of coexistence of heterogeneous TIME within a single individual with a pulmonary carcinoid tumor. This study may provide new insights into the mechanism of primary resistance to chemoimmunotherapy in pulmonary carcinoid tumors.https://doi.org/10.1111/1759-7714.13772Carcinoidcytotoxic T lymphocyte antigen 4 (CTLA‐4)heterogeneityimmune checkpoint inhibitor (ICI)neuroendocrine tumors (NET) |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Shinya Sakata Kosuke Imamura Yuka Tajima Yuiko Masuda Ryo Sato Chieko Yoshida Shinichiro Okamoto Sho Saeki Yusuke Tomita Takuro Sakagami |
spellingShingle |
Shinya Sakata Kosuke Imamura Yuka Tajima Yuiko Masuda Ryo Sato Chieko Yoshida Shinichiro Okamoto Sho Saeki Yusuke Tomita Takuro Sakagami Heterogeneous tumor‐immune microenvironments between primary and metastatic carcinoid tumors differentially respond to anti‐PD‐L1 antibody therapy Thoracic Cancer Carcinoid cytotoxic T lymphocyte antigen 4 (CTLA‐4) heterogeneity immune checkpoint inhibitor (ICI) neuroendocrine tumors (NET) |
author_facet |
Shinya Sakata Kosuke Imamura Yuka Tajima Yuiko Masuda Ryo Sato Chieko Yoshida Shinichiro Okamoto Sho Saeki Yusuke Tomita Takuro Sakagami |
author_sort |
Shinya Sakata |
title |
Heterogeneous tumor‐immune microenvironments between primary and metastatic carcinoid tumors differentially respond to anti‐PD‐L1 antibody therapy |
title_short |
Heterogeneous tumor‐immune microenvironments between primary and metastatic carcinoid tumors differentially respond to anti‐PD‐L1 antibody therapy |
title_full |
Heterogeneous tumor‐immune microenvironments between primary and metastatic carcinoid tumors differentially respond to anti‐PD‐L1 antibody therapy |
title_fullStr |
Heterogeneous tumor‐immune microenvironments between primary and metastatic carcinoid tumors differentially respond to anti‐PD‐L1 antibody therapy |
title_full_unstemmed |
Heterogeneous tumor‐immune microenvironments between primary and metastatic carcinoid tumors differentially respond to anti‐PD‐L1 antibody therapy |
title_sort |
heterogeneous tumor‐immune microenvironments between primary and metastatic carcinoid tumors differentially respond to anti‐pd‐l1 antibody therapy |
publisher |
Wiley |
series |
Thoracic Cancer |
issn |
1759-7706 1759-7714 |
publishDate |
2021-02-01 |
description |
A pulmonary carcinoid tumor is a rare tumor that lacks a validated therapeutic approach for unresectable disease. Understanding the intersite tumor‐immune heterogeneity is essential to harness the immune system for cancer therapy. However, little is known about the tumor‐immune microenvironment (TIME). Here, we describe a patient who had heterogeneous TIME between primary and metastatic carcinoid tumors which differentially responded to chemoimmunotherapy. A 72‐year‐old man was diagnosed with an advanced pulmonary carcinoid tumor. CT‐guided biopsies of lung and scapular tumors confirmed typical carcinoid (PD‐L1, 1%–24%) and atypical carcinoid tumors (PD‐L1, negative), respectively. Although the primary lung carcinoid tumor showed a partial response, the scapular tumor was significantly enlarged after two cycles of anti‐PD‐L1 antibody therapy in combination with carboplatin plus etoposide. We performed quantitative pathology imaging analysis with fluorescent multiplex immunohistochemistry. CD8+ T cell infiltration was detected in the PD‐L1‐positive primary lung tumor nest; however, it was mostly restrained in the stroma in a PD‐L1‐negative metastatic scapular tumor. Treg infiltrations into both tumor nests and stroma were detected in the lung tumor, which were not detected in the metastatic scapular tumor. This study provides the first evidence of coexistence of heterogeneous TIME within a single individual with a pulmonary carcinoid tumor. This study may provide new insights into the mechanism of primary resistance to chemoimmunotherapy in pulmonary carcinoid tumors. |
topic |
Carcinoid cytotoxic T lymphocyte antigen 4 (CTLA‐4) heterogeneity immune checkpoint inhibitor (ICI) neuroendocrine tumors (NET) |
url |
https://doi.org/10.1111/1759-7714.13772 |
work_keys_str_mv |
AT shinyasakata heterogeneoustumorimmunemicroenvironmentsbetweenprimaryandmetastaticcarcinoidtumorsdifferentiallyrespondtoantipdl1antibodytherapy AT kosukeimamura heterogeneoustumorimmunemicroenvironmentsbetweenprimaryandmetastaticcarcinoidtumorsdifferentiallyrespondtoantipdl1antibodytherapy AT yukatajima heterogeneoustumorimmunemicroenvironmentsbetweenprimaryandmetastaticcarcinoidtumorsdifferentiallyrespondtoantipdl1antibodytherapy AT yuikomasuda heterogeneoustumorimmunemicroenvironmentsbetweenprimaryandmetastaticcarcinoidtumorsdifferentiallyrespondtoantipdl1antibodytherapy AT ryosato heterogeneoustumorimmunemicroenvironmentsbetweenprimaryandmetastaticcarcinoidtumorsdifferentiallyrespondtoantipdl1antibodytherapy AT chiekoyoshida heterogeneoustumorimmunemicroenvironmentsbetweenprimaryandmetastaticcarcinoidtumorsdifferentiallyrespondtoantipdl1antibodytherapy AT shinichirookamoto heterogeneoustumorimmunemicroenvironmentsbetweenprimaryandmetastaticcarcinoidtumorsdifferentiallyrespondtoantipdl1antibodytherapy AT shosaeki heterogeneoustumorimmunemicroenvironmentsbetweenprimaryandmetastaticcarcinoidtumorsdifferentiallyrespondtoantipdl1antibodytherapy AT yusuketomita heterogeneoustumorimmunemicroenvironmentsbetweenprimaryandmetastaticcarcinoidtumorsdifferentiallyrespondtoantipdl1antibodytherapy AT takurosakagami heterogeneoustumorimmunemicroenvironmentsbetweenprimaryandmetastaticcarcinoidtumorsdifferentiallyrespondtoantipdl1antibodytherapy |
_version_ |
1724284050717278208 |