東華大學圖書館 |

語系: 繁體中文

說明(常見問題)

回圖書館首頁

手機版館藏查詢

登入

回首頁

切換: 標籤 | MARC模式 | ISBD

FindBook

Google Book

Amazon

博客來

Myeloid Cells in Systemic Immune Reactions During Cancer.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Myeloid Cells in Systemic Immune Reactions During Cancer./
作者:	Siwicki, Marie.
面頁冊數:	1 online resource (170 pages)
附註:	Source: Dissertations Abstracts International, Volume: 83-09, Section: B.
Contained By:	Dissertations Abstracts International83-09B.
標題:	Immunology. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=28962846click for full text (PQDT)
ISBN:	9798209894766

Myeloid Cells in Systemic Immune Reactions During Cancer.
Siwicki, Marie.

Myeloid Cells in Systemic Immune Reactions During Cancer. - 1 online resource (170 pages)

Source: Dissertations Abstracts International, Volume: 83-09, Section: B.

Thesis (Ph.D.)--Harvard University, 2022.

Includes bibliographical references

The immune system plays diverse roles during cancer-it can be protective against tumor growth, yet it may also foster cancer progression in some settings. Anti-cancer immunotherapy can simultaneously trigger both productive anti-tumor immune responses and undesired immune related adverse events (irAEs) in non-malignant tissues. How myeloid cells influence outcomes in cancer and therapy remains incompletely understood.Immunotherapies activate the immune system to fight cancer. When successful, they tend to foster a T helper type (Th)-1-polarized cellular immune response in the tumor, involving interleukin (IL)-12 production from myeloid cells (namely dendritic cells, or DCs) and interferon (IFN)-? production from lymphocytes. This response drives forward antigen-specific rejection of cancer cells. Whether similar processes drive irAEs in tumor-free tissues is not known. We therefore investigated mechanisms of irAEs in non-malignant tissue following anti-cancer immunotherapy. Using anti-CD40 treatment in mice as a model of Th1-promoting immunotherapy, we identified both similar and distinct processes occurring in cancerous and non-cancerous tissues. While Th1 cytokine activation was critical for both tumor control and toxicity of a tumor-free tissue site (the liver), the key myeloid cells players were distinct. DCs were required for tumor control; yet liver pathology depended on activation of tissue resident macrophages and a pathological neutrophil response. We found evidence of similar processes occurring in cancer patients experiencing irAEs. Our findings suggest distinct mechanisms of toxicity and anti-tumor immunity following Th1 immunotherapy.In a separate line of investigation, we established an approach for in vivo manipulation and study of neutrophils. Neutrophils can exert pro-tumoral functions, and they can exacerbate irAEs; therefore, targeting these cells could limit detrimental immune processes during cancer and immunotherapy. However, an appreciable level of neutrophil heterogeneity exists in both mice and humans, and important anti-tumoral neutrophil functions have also been identified. Therefore, it may be advantageous to selectively modulate molecular targets implicated in deleterious neutrophil functions, rather than targeting these cells holistically. Approaches to interrogate neutrophil-expressed genes in vivo are limited. We therefore developed a system to modulate neutrophil-associated targets in mice using CRISPR. This system enables stable and efficient editing of neutrophil-expressed genes, and it should be useful for interrogating the roles of defined neutrophil subpopulations during cancer.Together, these mechanistic studies and technical efforts hold implications for advancing our understanding of myeloid cell functions during cancer and immunotherapy. They may ultimately open doors to the development of therapeutic interventions based on modulating myeloid cell biology.

Electronic reproduction.
Ann Arbor, Mich. :
ProQuest,
2023

Mode of access: World Wide Web

ISBN: 9798209894766Subjects--Topical Terms:

611031
Immunology.
Subjects--Index Terms:

CancerIndex Terms--Genre/Form:

542853
Electronic books.

Myeloid Cells in Systemic Immune Reactions During Cancer.
LDR:04240nmm a2200385K 4500 001 2359717
005 20230917195225.5
006 m o d
007 cr mn ---uuuuu
008 241011s2022 xx obm 000 0 eng d
020 $a 9798209894766
035 $a (MiAaPQ)AAI28962846
035 $a AAI28962846
040 $a MiAaPQ $b eng $c MiAaPQ $d NTU
100 1 $a Siwicki, Marie. $3 3700337
245 1 0 $a Myeloid Cells in Systemic Immune Reactions During Cancer.
264 0 $c 2022
300 $a 1 online resource (170 pages)
336 $a text $b txt $2 rdacontent
337 $a computer $b c $2 rdamedia
338 $a online resource $b cr $2 rdacarrier
500 $a Source: Dissertations Abstracts International, Volume: 83-09, Section: B.
500 $a Advisor: Pittet, Mikael J.
502 $a Thesis (Ph.D.)--Harvard University, 2022.
504 $a Includes bibliographical references
520 $a The immune system plays diverse roles during cancer-it can be protective against tumor growth, yet it may also foster cancer progression in some settings. Anti-cancer immunotherapy can simultaneously trigger both productive anti-tumor immune responses and undesired immune related adverse events (irAEs) in non-malignant tissues. How myeloid cells influence outcomes in cancer and therapy remains incompletely understood.Immunotherapies activate the immune system to fight cancer. When successful, they tend to foster a T helper type (Th)-1-polarized cellular immune response in the tumor, involving interleukin (IL)-12 production from myeloid cells (namely dendritic cells, or DCs) and interferon (IFN)-? production from lymphocytes. This response drives forward antigen-specific rejection of cancer cells. Whether similar processes drive irAEs in tumor-free tissues is not known. We therefore investigated mechanisms of irAEs in non-malignant tissue following anti-cancer immunotherapy. Using anti-CD40 treatment in mice as a model of Th1-promoting immunotherapy, we identified both similar and distinct processes occurring in cancerous and non-cancerous tissues. While Th1 cytokine activation was critical for both tumor control and toxicity of a tumor-free tissue site (the liver), the key myeloid cells players were distinct. DCs were required for tumor control; yet liver pathology depended on activation of tissue resident macrophages and a pathological neutrophil response. We found evidence of similar processes occurring in cancer patients experiencing irAEs. Our findings suggest distinct mechanisms of toxicity and anti-tumor immunity following Th1 immunotherapy.In a separate line of investigation, we established an approach for in vivo manipulation and study of neutrophils. Neutrophils can exert pro-tumoral functions, and they can exacerbate irAEs; therefore, targeting these cells could limit detrimental immune processes during cancer and immunotherapy. However, an appreciable level of neutrophil heterogeneity exists in both mice and humans, and important anti-tumoral neutrophil functions have also been identified. Therefore, it may be advantageous to selectively modulate molecular targets implicated in deleterious neutrophil functions, rather than targeting these cells holistically. Approaches to interrogate neutrophil-expressed genes in vivo are limited. We therefore developed a system to modulate neutrophil-associated targets in mice using CRISPR. This system enables stable and efficient editing of neutrophil-expressed genes, and it should be useful for interrogating the roles of defined neutrophil subpopulations during cancer.Together, these mechanistic studies and technical efforts hold implications for advancing our understanding of myeloid cell functions during cancer and immunotherapy. They may ultimately open doors to the development of therapeutic interventions based on modulating myeloid cell biology.
533 $a Electronic reproduction. $b Ann Arbor, Mich. : $c ProQuest, $d 2023
538 $a Mode of access: World Wide Web
650 4 $a Immunology. $3 611031
650 4 $a Cellular biology. $3 3172791
650 4 $a Oncology. $3 751006
653 $a Cancer
653 $a Immunology
653 $a Immunotherapy
653 $a irAEs
655 7 $a Electronic books. $2 lcsh $3 542853
690 $a 0982
690 $a 0379
690 $a 0992
710 2 $a ProQuest Information and Learning Co. $3 783688
710 2 $a Harvard University. $b Medical Sciences. $3 3181716
773 0 $t Dissertations Abstracts International $g 83-09B.
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=28962846 $z click for full text (PQDT)