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FIGURE 2 from Tumor-infiltrating Leukocyte Profiling Defines Three Immune Subtypes of NSCLC with Distinct Signaling Pathways and Genetic Alterations

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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

Immune subtypes based on TIL profiling using FCM; NAT (n = 157), LUAD [85; Cold (n = 19), Myeloid (n = 36), CD8 (n = 30)], LUSQ [50; Cold (n = 14), Myeloid (n = 19), CD8 (n = 17)]. A, Heat map of cell densities and �45 of immune cells in NSCLC tumors and NATs. Each column represents a patient; data were normalized by Z-scores to indicate relative compositions of immune cells. Cell density is presented as the log of each cell type. �45 is presented as each immune cell type/CD45. Heat maps of cell density and �45 of TILs in LUAD (B) and LUSQ (C) tissues. D, Cell densities and �45 of immune cell types in LUAD and LUSQ immune subtypes. Top, Cell density indicates immune cells. Bottom, �45 indicates immune cells. AD.Cold, AD.Myeloid, and AD.CD8 are LUAD subtypes Cold, Myeloid, and CD8, respectively. SQ.Cold, SQ.Myeloid, and SQ.CD8 are LUSQ subtypes Cold, Myeloid, and CD8, respectively. E, IHC staining for CD8 in a representative case from immune subtypes. For CD8, FOXP3, CD20, and Ki67, the positivity of each marker was given as the number of total positive cell number within each tissue core. For CD33, the ratio of CD33-positive staining area per tissue area was calculated. F, Immune cell counts by IHC staining in lung cancer tissues. G, CD8+ T cell–attractant chemokine gene expression in immune subtypes.

Funding

Japan Agency for Medical Research and Development (AMED)

National Cancer Center Japan (NCC)

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

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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.

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