TY - JOUR
T1 - Regulation of antitumor immunity by inflammation-induced epigenetic alterations
AU - Karin, Michael
AU - Shalapour, Shabnam
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2022/1
Y1 - 2022/1
N2 - Chronic inflammation promotes tumor development, progression, and metastatic dissemination and causes treatment resistance. The accumulation of genetic alterations and loss of normal cellular regulatory processes are not only associated with cancer growth and progression but also result in the expression of tumor-specific and tumor-associated antigens that may activate antitumor immunity. This antagonism between inflammation and immunity and the ability of cancer cells to avoid immune detection affect the course of cancer development and treatment outcomes. While inflammation, particularly acute inflammation, supports T-cell priming, activation, and infiltration into infected tissues, chronic inflammation is mostly immunosuppressive. However, the main mechanisms that dictate the outcome of the inflammation-immunity interplay are not well understood. Recent data suggest that inflammation triggers epigenetic alterations in cancer cells and components of the tumor microenvironment. These alterations can affect and modulate numerous aspects of cancer development, including tumor growth, the metabolic state, metastatic spread, immune escape, and immunosuppressive or immunosupportive leukocyte generation. In this review, we discuss the role of inflammation in initiating epigenetic alterations in immune cells, cancer-associated fibroblasts, and cancer cells and suggest how and when epigenetic interventions can be combined with immunotherapies to improve therapeutic outcomes.
AB - Chronic inflammation promotes tumor development, progression, and metastatic dissemination and causes treatment resistance. The accumulation of genetic alterations and loss of normal cellular regulatory processes are not only associated with cancer growth and progression but also result in the expression of tumor-specific and tumor-associated antigens that may activate antitumor immunity. This antagonism between inflammation and immunity and the ability of cancer cells to avoid immune detection affect the course of cancer development and treatment outcomes. While inflammation, particularly acute inflammation, supports T-cell priming, activation, and infiltration into infected tissues, chronic inflammation is mostly immunosuppressive. However, the main mechanisms that dictate the outcome of the inflammation-immunity interplay are not well understood. Recent data suggest that inflammation triggers epigenetic alterations in cancer cells and components of the tumor microenvironment. These alterations can affect and modulate numerous aspects of cancer development, including tumor growth, the metabolic state, metastatic spread, immune escape, and immunosuppressive or immunosupportive leukocyte generation. In this review, we discuss the role of inflammation in initiating epigenetic alterations in immune cells, cancer-associated fibroblasts, and cancer cells and suggest how and when epigenetic interventions can be combined with immunotherapies to improve therapeutic outcomes.
KW - Antitumor immunity
KW - Epigenetics
KW - Immunotherapy
KW - Inflammation
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U2 - 10.1038/s41423-021-00756-y
DO - 10.1038/s41423-021-00756-y
M3 - Review article
C2 - 34465885
AN - SCOPUS:85114617603
SN - 1672-7681
VL - 19
SP - 59
EP - 66
JO - Cellular and Molecular Immunology
JF - Cellular and Molecular Immunology
IS - 1
ER -