A High Level of Tumor-Derived TGF-β Promotes Early Tumor Growth and Limits Subsequent Tumor Progression Independent of T Cell Immunity in Murine Colon Adenocarcinoma

Monoamine oxidase A (MAO-A) is an enzyme best known for its function in the brain, where it breaks down neurotransmitters and thereby influences mood and behavior. Small-molecule MAO inhibitors (MAOIs) have been developed and are clinically used for treating depression and other neurological disorders. However, the involvement of MAO-A in antitumor immunity has not been reported. Here, we observed induction of the Maoa gene in tumor-infiltrating immune cells. Maoa knockout mice exhibited enhanced antitumor T cell immunity and suppressed tumor growth. MAOI treatment significantly suppressed tumor growth in preclinical mouse syngeneic and human xenograft tumor models in a T cell–dependent manner. Combining MAOI and anti–PD-1 treatments generated synergistic tumor suppression effects. Clinical data correlation studies associated intratumoral MAOA expression with T cell dysfunction and decreased patient survival in a broad range of cancers. We further demonstrated that MAO-A restrains antitumor T cell immunity through controlling intratumoral T cell autocrine serotonin signaling. Together, these data identify MAO-A as an immune checkpoint and support repurposing MAOI antidepressants for cancer immunotherapy.

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Long-term inhibition of tumor growth by tumor necrosis factor in the absence of cachexia or T-cell immunity.

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.88.9.3535 ◽

1991 ◽

Vol 88 (9) ◽

pp. 3535-3539 ◽

Cited By ~ 53

Author(s):

M. N. Teng ◽

B. H. Park ◽

H. K. Koeppen ◽

K. J. Tracey ◽

B. M. Fendly ◽

...

Keyword(s):

T Cell ◽

Tumor Necrosis Factor ◽

Tumor Growth ◽

Tumor Necrosis ◽

T Cell Immunity ◽

Cell Immunity ◽

Inhibition Of Tumor Growth ◽

Necrosis Factor

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Immunosuppressive Effects of Myeloid-Derived Suppressor Cells in Cancer and Immunotherapy

Cells ◽

10.3390/cells10051170 ◽

2021 ◽

Vol 10 (5) ◽

pp. 1170

Author(s):

Mithunah Krishnamoorthy ◽

Lara Gerhardt ◽

Saman Maleki Maleki Vareki

Keyword(s):

T Cell ◽

Tumor Growth ◽

Cancer Immunotherapy ◽

Tumor Immunity ◽

Cancer Progression ◽

Suppressor Cells ◽

T Cell Immunity ◽

Myeloid Derived Suppressor Cells ◽

Cell Immunity ◽

Promote Tumor Growth

The primary function of myeloid cells is to protect the host from infections. However, during cancer progression or states of chronic inflammation, these cells develop into myeloid-derived suppressor cells (MDSCs) that play a prominent role in suppressing anti-tumor immunity. Overcoming the suppressive effects of MDSCs is a major hurdle in cancer immunotherapy. Therefore, understanding the mechanisms by which MDSCs promote tumor growth is essential for improving current immunotherapies and developing new ones. This review explores mechanisms by which MDSCs suppress T-cell immunity and how this impacts the efficacy of commonly used immunotherapies.

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Involvement of Thyroid Hormones in the Alterations of T-Cell Immunity and Tumor Progression Induced by Chronic Stress

Biological Psychiatry ◽

10.1016/j.biopsych.2008.12.013 ◽

2009 ◽

Vol 65 (11) ◽

pp. 935-942 ◽

Cited By ~ 22

Author(s):

Luciana Romina Frick ◽

Maximiliano Rapanelli ◽

Ursula Agnes Bussmann ◽

Alicia Juana Klecha ◽

Maria Laura Barreiro Arcos ◽

...

Keyword(s):

T Cell ◽

Thyroid Hormones ◽

Tumor Progression ◽

Chronic Stress ◽

T Cell Immunity ◽

Cell Immunity

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Novel Synthetic DNA Immunogens Targeting Latent Expressed Antigens of Epstein–Barr Virus Elicit Potent Cellular Responses and Inhibit Tumor Growth

Vaccines ◽

10.3390/vaccines7020044 ◽

2019 ◽

Vol 7 (2) ◽

pp. 44 ◽

Cited By ~ 2

Author(s):

Krzysztof Wojtak ◽

Alfredo Perales-Puchalt ◽

David B. Weiner

Keyword(s):

T Cell ◽

Tumor Growth ◽

Epstein Barr Virus ◽

Tumor Antigens ◽

Adult Population ◽

T Cell Immunity ◽

Nuclear Antigen ◽

Barr Virus ◽

Cell Immunity ◽

Epstein Barr

Infectious diseases are linked to 15%–20% of cancers worldwide. Among them, Epstein–Barr virus (EBV) is an oncogenic herpesvirus that chronically infects over 90% of the adult population, with over 200,000 cases of cancer and 150,000 cancer-related deaths attributed to it yearly. Acute EBV infection can present as infectious mononucleosis, and lead to the future onset of multiple cancers, including Burkitt lymphoma, Hodgkin lymphoma, nasopharyngeal carcinoma, and gastric carcinoma. Many of these cancers express latent viral genes, including Epstein–Barr virus nuclear antigen 1 (EBNA1) and latent membrane proteins 1 and 2 (LMP1 and LMP2). Previous attempts to create potent immunogens against EBV have been reported but generated mixed success. We designed novel Synthetic Consensus (SynCon) DNA vaccines against EBNA1, LMP1 and LMP2 to improve on the immune potency targeting important antigens expressed in latently infected cells. These EBV tumor antigens are hypothesized to be useful targets for potential immunotherapy of EBV-driven cancers. We optimized the genetic sequences for these three antigens, studied them for expression, and examined their immune profiles in vivo. We observed that these immunogens generated unique profiles based on which antigen was delivered as the vaccine target. EBNA1vax and LMP2Avax generated the most robust T cell immunity. Interestingly, LMP1vax was a very weak immunogen, generating very low levels of CD8 T cell immunity both as a standalone vaccine and as part of a trivalent vaccine cocktail. LMP2Avax was able to drive immunity that impacted EBV-antigen-positive tumor growth. These studies suggest that engineered EBV latent protein vaccines deserve additional study as potential agents for immunotherapy of EBV-driven cancers.

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