title: Cancer-induced immunosuppressive cascades and their reversal by molecular-targeted therapy.
abstract: Immunological status in tumor tissues varies among patients. Infiltration of memory-type CD8(+) T cells into tumors correlates with prognosis of patients with various cancers. However, the mechanism of the differential CD8(+) T cell infiltration has not been well investigated. In general, tumor-associated microenvironments, including tumor and sentinel lymph nodes, are under immunosuppressive conditions such that the immune system is not able to eliminate cancer cells without immune-activating interventions. Constitutive activation of various signaling pathways in human cancer cells triggers multiple immunosuppressive cascades that involve various cytokines, chemokines, and immunosuppressive cells. Signaling pathway inhibitors could inhibit these immunosuppressive cascades by acting on either cancer or immune cells, or both. In addition, common signaling mechanisms are often utilized for multiple hallmarks of cancer (e.g., cell proliferation/survival, invasion/metastasis, and immunosuppression). Therefore, targeting these common signaling pathways may be an attractive strategy for cancer therapy including immunotherapy.
authors: Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan. yutakawa@z5.keio.jp
authors: Yutaka
authors: Y
authors: Kawakami
authors: Tomonori
authors: T
authors: Yaguchi
authors: Hidetoshi
authors: H
authors: Sumimoto
authors: Chie
authors: C
authors: Kudo-Saito
authors: Nobuo
authors: N
authors: Tsukamoto
authors: Tomoko
authors: T
authors: Iwata-Kajihara
authors: Shoko
authors: S
authors: Nakamura
authors: Hiroshi
authors: H
authors: Nishio
authors: Ryosuke
authors: R
authors: Satomi
authors: Asuka
authors: A
authors: Kobayashi
authors: Mayuri
authors: M
authors: Tanaka
authors: Jeong Hoon
authors: JH
authors: Park
authors: Hajime
authors: H
authors: Kamijuku
authors: Takahiro
authors: T
authors: Tsujikawa
authors: Naoshi
authors: N
authors: Kawamura
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007167:Immunotherapy / Q000379:methods*; D020935:MAP Kinase Signaling System; D051379:Mice; D058990:Molecular Targeted Therapy / Q000379:methods*; D016328:NF-kappa B / Q000378:metabolism; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy; D048493:Proto-Oncogene Proteins B-raf / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D051176:beta Catenin / Q000378:metabolism
chemical_list: D007166:Immunosuppressive Agents; D016328:NF-kappa B; D050796:STAT3 Transcription Factor; D051176:beta Catenin; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf