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Mononuclear Phagocyte Modulation of ...

Kubli, Shawn P.

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Mononuclear Phagocyte Modulation of the Tumor Microenvironment and Control of Anti-tumor Immunity.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Mononuclear Phagocyte Modulation of the Tumor Microenvironment and Control of Anti-tumor Immunity./
作者:	Kubli, Shawn P.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2019,
面頁冊數:	282 p.
附註:	Source: Dissertations Abstracts International, Volume: 81-04, Section: B.
Contained By:	Dissertations Abstracts International81-04B.
標題:	Cellular biology. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=13426434
ISBN:	9781085762427

Mononuclear Phagocyte Modulation of the Tumor Microenvironment and Control of Anti-tumor Immunity.
Kubli, Shawn P.

Mononuclear Phagocyte Modulation of the Tumor Microenvironment and Control of Anti-tumor Immunity. - Ann Arbor : ProQuest Dissertations & Theses, 2019 - 282 p.

Source: Dissertations Abstracts International, Volume: 81-04, Section: B.

Thesis (Ph.D.)--University of Toronto (Canada), 2019.

This item must not be sold to any third party vendors.

Tumors are heterogeneously comprised of various cell types that make up a complex tissue-like structure, where cancer cells interact with various non-malignant cells. Immune cells represent one of these non-malignant cell types, and are particularly suitable as targets for anti-cancer therapeutics. Therapeutics that target the immune system (Immunotherapeutics), which are currently in clinical application, aim to restore immune responses to cancer cells by inhibiting the immune checkpoints that dampen lymphocyte responses. The efficacy of these immunotherapeutics results in good prognosis for some patients. Unfortunately, there are many non-responders, and we are only now just starting to discern the mechanisms that govern response efficacy. Targeting these immune checkpoints, with αPD-1 and αCTLA-4 monoclonal antibodies, restores anti-tumor effector function to dysfunctional tumor infiltrating lymphocytes, and facilitates the reduction of regulatory T cells. However, there are other aspects of tumor immunology that are unaffected by these drugs. Combinatorial treatment strategies that amplify the effects of current immune modulating drugs are thus predicted to enhance response efficacy.It is well established that myeloid cells contribute to oncogenesis, but how the constellation of receptors they express regulates their functions within the tumor microenvironment is less clear. Furthermore, cells of the mononuclear phagocytic system have the potential to function in a pro-tumoral capacity, or to promote anti-tumor immunity for cancer cell elimination. Here we demonstrate that autocrine and paracrine EGFR signaling between intratumoral macrophages and cancer cells facilitates tumorigenesis through macrophage mediated trophic support. Specifically, we show a novel AhR-AREG axis facilitates maintenance of the tumor microenvironment in BRCA1-associated breast cancer. Alternatively, in a syngeneic melanoma model we illustrate that Toso (FCMR), the putative receptor for soluble IgM, modulates myeloid cell responses to cancer to inhibit anti-tumor immunity. Furthermore, Toso negatively regulated the activation and migratory capacity of skin-associated myeloid cells in vivo, and bone-marrow derived dendritic cell-dependent T cell activation in vitro. Importantly, preliminary data indicates therapeutically targeting Ahr in BRCA1-associated cancers, or Toso in melanoma, may improve patient prognosis. Overall, these results suggest that targeting myeloid cell function within the TME represents a potential therapeutic avenue for bolstering current checkpoint immunotherapeutics.

ISBN: 9781085762427Subjects--Topical Terms:

3172791
Cellular biology.
Subjects--Index Terms:

Immune cells

Mononuclear Phagocyte Modulation of the Tumor Microenvironment and Control of Anti-tumor Immunity.
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