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Cancer‐induced immunosuppressive cascades and their reversal by molecular‐targeted therapy
Author(s) -
Kawakami Yutaka,
Yaguchi Tomonori,
Sumimoto Hidetoshi,
KudoSaito Chie,
Tsukamoto Nobuo,
IwataKajihara Tomoko,
Nakamura Shoko,
Nishio Hiroshi,
Satomi Ryosuke,
Kobayashi Asuka,
Tanaka Mayuri,
Park Jeong Hoon,
Kamijuku Hajime,
Tsujikawa Takahiro,
Kawamura Naoshi
Publication year - 2013
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/nyas.12094
Subject(s) - immune system , cancer research , immunosuppression , immunotherapy , chemokine , immunology , tumor microenvironment , cd8 , cancer , cancer immunotherapy , signal transduction , metastasis , medicine , cancer cell , biology , microbiology and biotechnology
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.