DC Field | Value | Language |
---|---|---|
dc.contributor.advisor | Shin, Eui-Cheol | - |
dc.contributor.advisor | 신의철 | - |
dc.contributor.author | Kim, Kyung Hwan | - |
dc.date.accessioned | 2021-05-11T19:43:25Z | - |
dc.date.available | 2021-05-11T19:43:25Z | - |
dc.date.issued | 2020 | - |
dc.identifier.uri | http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=907100&flag=dissertation | en_US |
dc.identifier.uri | http://hdl.handle.net/10203/283563 | - |
dc.description | 학위논문(박사) - 한국과학기술원 : 의과학대학원, 2020.2,[iv, 60 p. :] | - |
dc.description.abstract | Blockade of programmed death-1 (PD-1) reinvigorates exhausted CD8+ T cells, resulting in tumor regression in cancer patients. Recently, reinvigoration of exhausted CD8+ T cells following PD-1 blockade was shown to be CD28-dependent in mouse models. Herein, I examined the role of CD28 in anti-PD-1-induced human T-cell reinvigoration using tumor-infiltrating CD8+ T cells (CD8+ TILs) obtained from non-small cell lung cancer patients. Single cell analysis demonstrated a distinct expression pattern of CD28 between mouse and human CD8+ TILs. Furthermore, I found that human CD28+CD8+, but not CD28–CD8+ TILs, responded to PD-1 blockade irrespective of B7/CD28 blockade, indicating that CD28 co-stimulation in human CD8+ TILs is dispensable for PD-1 blockade-induced reinvigoration, but loss of CD28 expression rather serves as a marker of anti-PD-1-unresponsive CD8+ TILs. Transcriptionally and phenotypically, PD-1 blockade-unresponsive human CD28–PD-1+CD8+ TILs exhibited characteristics of terminally exhausted CD8+ T cells with low TCF1 expression. Notably, CD28–PD-1+CD8+ TILs had preserved machinery to respond to IL-15, and IL-15 treatment enhanced proliferation of CD28–PD-1+CD8+ TILs as well as CD28+PD-1+CD8+ TILs. Taken together, I demonstrate loss of CD28 expression as a marker of PD-1 blockade-unresponsive human CD8+ TILs with TCF1– signature and provide mechanistic insights into combining IL-15 with anti-PD-1. | - |
dc.language | eng | - |
dc.publisher | 한국과학기술원 | - |
dc.subject | anti-PD-1▼aT cells▼aunresponsiveness▼aCD28▼aTCF1▼ainterleukin-15 | - |
dc.subject | 항 PD-1▼aT 세포▼a저항성▼aCD28▼aTCF1▼a인터루킨-15 | - |
dc.title | Characterizing anti-programmed death-1-resistant $CD8^+$ T cells and overcoming resistance | - |
dc.title.alternative | 항 PD-1 치료 저항성 $CD8^+$ T 세포 특성 규명 및 저항성 극복 방안 연구 | - |
dc.type | Thesis(Ph.D) | - |
dc.identifier.CNRN | 325007 | - |
dc.description.department | 한국과학기술원 :의과학대학원, | - |
dc.contributor.alternativeauthor | 김경환 | - |
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