Open AccessTet2 deficiency in immune cells exacerbates tumor progression by increasing angiogenesis in a lung cancer model
Author(s) -
Nguyen Yen T. M.,
Fujisawa Manabu,
Nguyen Tran B.,
Suehara Yasuhito,
Sakamoto Tatsuhiro,
Matsuoka Ryota,
Abe Yoshiaki,
Fukumoto Kota,
Hattori Keiichiro,
Noguchi Masayuki,
Matsubara Daisuke,
Chiba Shigeru,
SakataYanagimoto Mamiko
Publication year - 2021
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.15165
Subject(s) - angiogenesis , s100a9 , immune system , biology , cancer research , lung cancer , myeloid , haematopoiesis , cancer , immunology , tumor progression , medicine , inflammation , pathology , stem cell , genetics
Immune cells harboring somatic mutations reportedly infiltrate cancer tissues in patients with solid cancers and accompanying clonal hematopoiesis. Loss‐of‐function TET2 mutations are frequently observed in clonal hematopoiesis in solid cancers. Here, using a mouse lung cancer model, we evaluated the activity of Tet2 ‐deficient immune cells in tumor tissues. Myeloid‐specific Tet2 deficiency enhanced tumor growth in mice relative to that seen in controls. Single‐cell sequencing analysis of immune cells infiltrating tumors showed relatively high expression of S100a8/S100a9 in Tet2 ‐deficient myeloid subclusters. In turn, treatment with S100a8/S100a9 promoted Vegfa production by cancer cells, leading to a marked increase in the tumor vasculature in Tet2 ‐deficient mice relative to controls. Finally, treatment of Tet2 ‐deficient mice with an antibody against Emmprin, a known S100a8/S100a9 receptor, suppressed tumor growth. These data suggest that immune cells derived from TET2 ‐mutated clonal hematopoiesis exacerbate lung cancer progression by promoting tumor angiogenesis and may provide a novel therapeutic target for lung cancer patients with TET2 ‐mutated clonal hematopoiesis.