PMID- 19903840 OWN - NLM STAT- MEDLINE DCOM- 20091221 LR - 20220309 IS - 1538-7445 (Electronic) IS - 0008-5472 (Print) IS - 0008-5472 (Linking) VI - 69 IP - 23 DP - 2009 Dec 1 TI - Recognition and killing of brain tumor stem-like initiating cells by CD8+ cytolytic T cells. PG - 8886-93 LID - 10.1158/0008-5472.CAN-09-2687 [doi] AB - Solid tumors contain a subset of stem-like cells that are resistant to the cytotoxic effects of chemotherapy/radiotherapy, but their susceptibility to cytolytic T lymphocyte (CTL) effector mechanisms has not been well characterized. Using a panel of early-passage human brain tumor stem/initiating cell (BTSC) lines derived from high-grade gliomas, we show that BTSCs are subject to immunologic recognition and elimination by CD8(+) CTLs. Compared with serum-differentiated CD133(low) tumor cells and established glioma cell lines, BTSCs are equivalent with respect to expression levels of HLA class I and ICAM-1, similar in their ability to trigger degranulation and cytokine synthesis by antigen-specific CTLs, and equally susceptible to perforin-dependent CTL-mediated cytolysis. BTSCs are also competent in the processing and presentation of antigens as evidenced by the killing of these cells by CTL when antigen is endogenously expressed. Moreover, we show that CTLs can eliminate all BTSCs with tumor-initiating activity in an antigen-specific manner in vivo. Current models predict that curative therapies for many cancers will require the elimination of the stem/initiating population, and these studies lay the foundation for developing immunotherapeutic approaches to eradicate this tumor population. FAU - Brown, Christine E AU - Brown CE AD - Department of Cancer Immunotherapeutics, Division of Neurosurgery, City of Hope National Medical Center, Duarte, California 91010, USA. FAU - Starr, Renate AU - Starr R FAU - Martinez, Catalina AU - Martinez C FAU - Aguilar, Brenda AU - Aguilar B FAU - D'Apuzzo, Massimo AU - D'Apuzzo M FAU - Todorov, Ivan AU - Todorov I FAU - Shih, Chu-Chih AU - Shih CC FAU - Badie, Behnam AU - Badie B FAU - Hudecek, Michael AU - Hudecek M FAU - Riddell, Stanley R AU - Riddell SR FAU - Jensen, Michael C AU - Jensen MC LA - eng GR - M01 RR000043-450856/RR/NCRR NIH HHS/United States GR - M01 RR000043-475806/RR/NCRR NIH HHS/United States GR - M01 RR000043-475779/RR/NCRR NIH HHS/United States GR - M01 RR000043-440856/RR/NCRR NIH HHS/United States GR - M01 RR00043/RR/NCRR NIH HHS/United States GR - P30 CA 33572/CA/NCI NIH HHS/United States GR - M01 RR000043/RR/NCRR NIH HHS/United States GR - P30 CA033572-200003/CA/NCI NIH HHS/United States GR - P30 CA033572/CA/NCI NIH HHS/United States GR - R01 CA103959/CA/NCI NIH HHS/United States GR - R01 CA103959-03/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20091110 PL - United States TA - Cancer Res JT - Cancer research JID - 2984705R RN - 0 (AC133 Antigen) RN - 0 (Antigens, CD) RN - 0 (Glycoproteins) RN - 0 (HLA-A2 Antigen) RN - 0 (PROM1 protein, human) RN - 0 (Peptides) RN - 0 (Prom1 protein, mouse) SB - IM MH - AC133 Antigen MH - Animals MH - Antigen Presentation MH - Antigens, CD/biosynthesis/immunology MH - Brain Neoplasms/*immunology/pathology MH - Cell Death/immunology MH - Cell Line, Tumor MH - Glioma/*immunology/pathology MH - Glycoproteins/biosynthesis/immunology MH - HLA-A2 Antigen/immunology MH - Humans MH - Mice MH - Mice, Inbred NOD MH - Mice, SCID MH - Neoplastic Stem Cells/*immunology/pathology MH - Peptides/immunology MH - T-Lymphocytes, Cytotoxic/*immunology MH - Transplantation, Heterologous PMC - PMC2789196 MID - NIHMS150326 EDAT- 2009/11/12 06:00 MHDA- 2009/12/22 06:00 PMCR- 2010/12/01 CRDT- 2009/11/12 06:00 PHST- 2009/11/12 06:00 [entrez] PHST- 2009/11/12 06:00 [pubmed] PHST- 2009/12/22 06:00 [medline] PHST- 2010/12/01 00:00 [pmc-release] AID - 0008-5472.CAN-09-2687 [pii] AID - 10.1158/0008-5472.CAN-09-2687 [doi] PST - ppublish SO - Cancer Res. 2009 Dec 1;69(23):8886-93. doi: 10.1158/0008-5472.CAN-09-2687. Epub 2009 Nov 10.