Fig. S2 from Tumor-infiltrating Leukocyte Profiling Defines Three Immune Subtypes of NSCLC with Distinct Signaling Pathways and Genetic Alterations

Aoki, Kazunori; Nishito, Yukari; Motoi, Noriko; Arai, Yasuhito; Hiraoka, Nobuyoshi; Shibata, Tatsuhiro; Sonobe, Yukiko; Kayukawa, Yoko; Hashimoto, Eri; Takahashi, Mina; Fujii, Etsuko; Nishizawa, Takashi; Fukuda, Hironori; Ohashi, Kana; Arai, Kosuke; Mizoguchi, Yukihiro; Yoshida, Yukihiro; Watanabe, Shun-ichi; Yamashita, Makiko; Kitano, Shigehisa; Sakamoto, Hiromi; Nagata, Yuki; Mitsumori, Risa; Ozaki, Kouichi; Niida, Shumpei; Kanai, Yae; Hirayama, Akiyoshi; Soga, Tomoyoshi; Maruyama, Toru; Tsukada, Keisuke; Yabuki, Nami; Shimada, Mei; Kitazawa, Takehisa; Natori, Osamu; Sawada, Noriaki; Kato, Atsuhiko; Yoshida, Teruhiko; Yasuda, Kazuki; Mizuno, Hideaki; Tsunoda, Hiroyuki; Ochiai, Atsushi

doi:10.1158/2767-9764.23508994.v1

Fig. S2 from Tumor-infiltrating Leukocyte Profiling Defines Three Immune Subtypes of NSCLC with Distinct Signaling Pathways and Genetic Alterations

https://doi.org/10.1158/2767-9764.23508994

journal contribution

posted on 2023-06-13, 14:20 authored by Kazunori Aoki, Yukari Nishito, Noriko Motoi, Yasuhito Arai, Nobuyoshi Hiraoka, Tatsuhiro Shibata, Yukiko Sonobe, Yoko Kayukawa, Eri Hashimoto, Mina Takahashi, Etsuko Fujii, Takashi Nishizawa, Hironori Fukuda, Kana Ohashi, Kosuke Arai, Yukihiro Mizoguchi, Yukihiro Yoshida, Shun-ichi Watanabe, Makiko Yamashita, Shigehisa Kitano, Hiromi Sakamoto, Yuki Nagata, Risa Mitsumori, Kouichi Ozaki, Shumpei Niida, Yae Kanai, Akiyoshi Hirayama, Tomoyoshi Soga, Toru Maruyama, Keisuke Tsukada, Nami Yabuki, Mei Shimada, Takehisa Kitazawa, Osamu Natori, Noriaki Sawada, Atsuhiko Kato, Teruhiko Yoshida, Kazuki Yasuda, Hideaki Mizuno, Hiroyuki Tsunoda, Atsushi Ochiai

<p>Representative polychromatic dot plots demonstrating the gating strategy employed to identify the immune cell profile of TILs in NSCLC. Starting at the top left, the initial gate was to obtain live cells; next, leukocytes (CD45+) and epithelial cells (CD326+) were gated; finally, CD3+ cells and CD3- cells were separated. For CD3+ cells, a size gate was applied to identify NKT cells (CD3+ CD56+), CD3+CD4+ and CD3+CD8+ T cells. T cell subsets are displayed, including naïve (CD45RA+CD197+), central memory (CM: CD45RA-CD197+), effector memory (EM: CD45RA-CD197-), and effector memory cells re-expressing CD45RA (EMRA: CD45RA+CD197-). FOXP3-expressing CD4+ T cells were gated on CD4+ T cells: naïve Treg (Fr. I: CD45RA+FOXP3lo), effector Treg (Fr. II: CD45RA-FOXP3hi), and non-Treg (Fr. III: CD45RA-FOXP3lo). For CD3- cells, a size gate was applied to identify B (CD3-CD19+) and NK cells (CD3-CD56+). The myeloid cell lineage was also gated on CD3- cells: conventional DC (HLA-DR+CD11c+), plasmacytoid DC (HLA-DR+CD11c-CD123+), macrophage (CD68+SSChi) and monocytic MDSC (HLA-DRlo CD14+CD11b+CD33+). Ki-67-expressing cells were gated in CD8+NKT, CD4+NKT, CD4+T (NT, CM, EM, EMRA), CD8+T (NT, CM, EM, EMRA), Treg, B, NK, and mMDSC. PD-1-expressing cells were gated in CD4+T (naive, CM, EM, EMRA), CD8+T (naive, CM, EM, EMRA) and Treg cells. PD-L1-expressing cells were gated in CD8+T (NT, CM, EM, EMRA), and mMDSC. CTLA-4-expressing cells were gated in Treg cells.</p>

Funding

Japan Agency for Medical Research and Development (AMED)

National Cancer Center Japan (NCC)

MEXT | Japan Society for the Promotion of Science (JSPS)

History

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DOI - Is supplement to Tumor-infiltrating Leukocyte Profiling Defines Three Immune Subtypes of NSCLC with Distinct Signaling Pathways and Genetic Alterations

ARTICLE ABSTRACT

The precise TIL profiling classified NSCLC into novel three immune subtypes that correlates with patient outcome, identifying subtype-specific molecular pathways and genomic alterations that should play important roles in constructing subtype-specific immune tumor microenvironments. These classifications of NSCLC based on TIL status are useful for developing personalized immune therapies for NSCLC.