FIGURE 4 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

Immunologic characteristics of immune subtypes based on TIL profiling. Numbers of cases analyzed using RNA-seq were LUAD (n = 72; Cold, n = 14; Myeloid, n = 33; CD8, n = 25) and LUSQ (n = 44; Cold, n = 10; Myeloid, n = 18; CD8, n = 16). A, Expression of IFNγ and granzyme B as a function of immune subtype. B, Scores of type I IFN and IFNγ signatures as a function of immune subtype. Expression levels and scores were obtained from RNA-seq. C, Boxplots showing Shannon entropies of canonical TCR repertoires (TCRα, TCRβ, TCRδ, and TCRγ) as a function of immune subtype. D, Expression of immune checkpoint molecules as a function of immune subtype. PDCD1, CD274, HAVCR2, and LAG3 expression levels are obtained from RNA-seq. E and F, Radar plots showing immunograms of immune subtypes; axes were generated with the IGS. Median IGS is plotted in red. LUAD (E). LUSQ (F).

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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Keywords

Lung Cancer Tumor Microenvironment Immune cells and the microenvironment Cytokines and the microenvironment Immunology Immune responses to cancer

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