scholarly journals Oxidative Phosphorylation Induces De Novo Expression of the MHC Class I in Tumor Cells through the ERK5 Pathway

2010 ◽  
Vol 185 (6) ◽  
pp. 3498-3503 ◽  
Author(s):  
Seyma Charni ◽  
Geoffroy de Bettignies ◽  
Moeez G. Rathore ◽  
Juan I. Aguiló ◽  
Peter J. van den Elsen ◽  
...  
Keyword(s):  
Oxidative Phosphorylation ◽  
Tumor Cells ◽  
Mhc Class I ◽  
De Novo ◽  
Class I

scholarly journals Cross-priming of minor histocompatibility antigen-specific cytotoxic T cells upon immunization with the heat shock protein gp96.

1995 ◽  
Vol 182 (3) ◽  
pp. 885-889 ◽  
Author(s):  
D Arnold ◽  
S Faath ◽  
H Rammensee ◽  
H Schild
Keyword(s):  
Heat Shock ◽  
Heat Shock Proteins ◽  
Heat Shock Protein ◽  
Tumor Cells ◽  
Mhc Class I ◽  
Donor Cell ◽  
Class I ◽  
Heat Shock Protein Gp96 ◽  
Shock Proteins

Vaccination of mice with heat shock proteins isolated from tumor cells induces immunity to subsequent challenge with those tumor cells the heat shock protein was isolated from but not with other tumor cells (Udono, H., and P.K. Srivastava. 1994. J. Immunol. 152:5398-5403). The specificity of this immune response is caused by tumor-derived peptides bound to the heat shock proteins (Udono., H., and P.K. Srivastava. 1993. J. Exp. Med. 178:1391-1396). Our experiments show that a single immunization with the heat shock protein gp96 isolated from beta-galactosidase (beta-gal) expressing P815 cells (of DBA/2 origin) induces cytotoxic T lymphocytes (CTLs) specific for beta-gal, in addition to minor H antigens expressed by these cells. CTLs can be induced in mice that are major histocompatibility complex (MHC) identical to the gp96 donor cells (H-2d) as well as in mice with a different MHC (H-2b). Thus gp96 is able to induce "cross priming" (Matzinger, P., and M.J. Bevan. 1977. Cell. Immunol. 33:92-100), indicating that gp96-associated peptides are not limited to the MHC class I ligands of the gp96 donor cell. Our data confirm the notion that samples of all cellular antigens presentable by MHC class I molecules are represented by peptides associated with gp96 molecules of that cell, even if the fitting MHC molecule is not expressed. In addition, we extend previous reports on the in vivo immunogenicity of peptides associated gp96 molecules to two new groups of antigens, minor H antigens, and proteins expressed in the cytosol.

Central Role of the Antigen-Presentation and Interferon-γ Pathways in Resistance to Immune Checkpoint Blockade

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Annette Paschen ◽  
Ignacio Melero ◽  
Antoni Ribas
Keyword(s):  
Antigen Presentation ◽  
Tumor Cells ◽  
Mhc Class I ◽  
Cancer Biology ◽  
Interleukin 2 ◽  
Interferon Γ ◽  
Class I ◽  
Annual Review ◽  
Publication Date ◽  
Type I

Resistance to immunotherapy is due in some instances to the acquired stealth mechanisms of tumor cells that lose expression of MHC class I antigen–presenting molecules or downregulate their class I antigen–presentation pathways. Most dramatically, biallelic β2-microglobulin (B2M) loss leads to complete loss of MHC class I expression and to invisibility to CD8+ T cells. MHC class I expression and antigen presentation are potently upregulated by interferon-γ (IFNγ) in a manner that depends on IFNγ receptor (IFNGR) signaling via JAK1 and JAK2. Mutations in these molecules lead to IFNγ unresponsiveness and mediate loss of recognition and killing by cytotoxic T lymphocytes. Loss of MHC class I augments sensitivity of tumor cells to be killed by natural killer (NK) lymphocytes, and this mechanism could be exploited to revert resistance, for instance, with interleukin-2 (IL-2)-based agents. Moreover, in some experimental models, potent local type I interferon responses, such as those following intratumoral injection of Toll-like receptor 9 (TLR9) or TLR3 agonists, revert resistance due to mutations of JAKs. Expected final online publication date for the Annual Review of Cancer Biology, Volume 6 is April 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Lymphoid Tumors ofXenopus laeviswith Different Capacities for Growth in Larvae and Adults

1994 ◽  
Vol 3 (4) ◽  
pp. 297-307 ◽  
Author(s):  
Jacques Robert ◽  
Chantal Guiet ◽  
Louis Du Pasquier
Keyword(s):  
Cell Surface ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Mhc Class I ◽  
Mhc Class Ii ◽  
Cell Lineage ◽  
Cell Types ◽  
Class Ii ◽  
Class I ◽  
Specific Marker

Three new lymphoid tumors offering an assortment of variants in terms of MHC class I expressions, MHC class II expression, and Ig gene transcription have been discovered in the amphibianXenopus. One was developed in an individual of the isogenic LG15 clone (LG15/0), one in a frog of the LG15/40 clone (derived from a small egg recombinant of LG15), and one (ff-2) in a maleffsib of the individual in which MAR1, the first lymphoid tumor in Xenopus was found 2 years ago. These tumors developed primarily as thymus outgrowths and were transplantable in histocompatible tadpoles but not in nonhistocompatible hosts. Whereas LG15/0 and LG15/40 tumor cells also grow in adult LG15 frogs, theff-2 tumor, like the MAR1 cell line, is rejected by adultffanimals. Using flow cytometry with fluorescence-labeled antibodies and immunoprecipitation analysis, we could demonstrate that, like MAR1, these three new tumors express on their cell surface lymphopoietic markers recognized by mAbs FIF6 and RC47, as well as T-cell lineage markers recognized by mAbs AM22 (CD8-1ike) and X21.2, but not by immunologobulin (Ig) nor MHC class II molecules. Another lymphocyte-specific marker AM15 is expressed by 15/0 and 15/40 but notff-2 tumor cells. Theff-2 tumor cell expresses MHC class molecule in association withβ2-microglobulin on the surface, 15/40 cells contain cytoplasmic Iαchain that is barely detected at the cell surface by fluocytometry, and 15/0 cells do not synthesize class Iαchain at all. The three new tumors all produce large amounts of IgM mRNA of two different sizes but no Ig protein on the membrane nor in the cytoplasm. All tumor cell types synthesize large amount of Myc mRNA and MHC class I-like transcripts considered to be non classical.

Tumor-specific recognition of human myeloma cells by idiotype-induced CD8+ T cells

Blood ◽  
2000 ◽  
Vol 96 (8) ◽  
pp. 2828-2833 ◽  
Author(s):  
Yiwen Li ◽  
Maurizio Bendandi ◽  
Yuping Deng ◽  
Cynthia Dunbar ◽  
Nikhil Munshi ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tumor Cells ◽  
Mhc Class I ◽  
Cd8 T Cells ◽  
Class I ◽  
Specific Lysis ◽  
Myeloma Cells ◽  
Id Protein ◽  
Human Myeloma Cells

Immunoglobulin secreted by myeloma cells contains a unique antigenic determinant (idiotype [Id]) that may serve as a tumor-specific antigen. Although Id-protein–specific T-cell responses have been reported in patients with myeloma, it is not known whether primary myeloma tumor cells can present naturally processed Id peptides on their surface as a target. We immunized 2 healthy human stem-cell donors with Id proteins from their recipients. T cells from the immunized donors released high levels of T-helper 1–type cytokines in response to stimulation with myeloma cells from their recipients. The T-cell–mediated cytokine response to tumor cells was blocked by a major histocompatibility complex (MHC) class I monoclonal antibody, whereas the response to soluble Id protein was dependent on MHC class II. To investigate whether Id-specific CD8+ T cells can recognize and kill autologous myeloma cells, we generated T cells from peripheral blood mononuclear cells from a third patient with myeloma by means of in vitro stimulation with autologous dendritic cells pulsed with Id protein. Tumor-specific lysis of myeloma cells was demonstrated by the lack of killing of autologous nonmalignant B cells or natural killer–sensitive K562 cells. Lysis of autologous myeloma targets was restricted by MHC class I molecules. These data represent the first report of class I–restricted T-cell recognition of fresh autologous myeloma targets and formally demonstrate that human myeloma cells can serve as targets of an Id-specific T-cell response.

DS-8201a, a HER2-targeting antibody-drug conjugate, to elicit immune responses and benefits in combination with an anti-PD-1 antibody.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1031-1031 ◽  
Author(s):  
Tomomi Nakayama Iwata ◽  
Chiaki Ishii ◽  
Yusuke Ogitani ◽  
Teiji Wada ◽  
Toshinori Agatsuma
Keyword(s):  
Mouse Model ◽  
Immune Responses ◽  
Tumor Cells ◽  
Mhc Class I ◽  
Antitumor Efficacy ◽  
Class I ◽  
Antibody Drug Conjugate ◽  
Antitumor Effects ◽  
Drug Conjugate ◽  
Antibody Drug

1031 Background: DS-8201a, a HER2-targeting antibody–drug conjugate (ADC), with a topoisomerase I inhibitor, exatecan drivative (DX-8951 derivative, DXd) has been shown to have antitumor effects in preclinical xenograft models and clinical trials, but the involvement of the immune system in the antitumor efficacy of DS-8201a has not been elucidated yet. Methods: The antitumor efficacy of DS-8201a individually and in combination with an anti-PD-1 antibody was determined in a syngeneic mouse model with human HER2-expressing CT26.WT (CT26.WT-hHER2) cells. Mice whose tumors had been cured by DS-8201a treatment were rechallenged with CT26.WT-hHER2 cells; their splenocytes were co-cultured with CT26.WT-hHER2 or CT26.WT-mock cells, and IFN-g secretion by these cells was determined. To investigate effects of DXd and DS-8201a on dendritic cells (DCs), the expression of DC markers on bone marrow derived DCs (BMDCs) and intratumoral DCs was analyzed by flow cytometry. Furthermore, MHC class I and PD-L1 expression on tumor cells was analyzed. Results: At a weekly dosage of 10 mg/kg, DS-8201a showed significant antitumor effects in the mouse model. Mice whose tumors had been cured by DS-8201a treatment rejected the rechallenge with CT26.WT-hHER2 cells, and splenocytes from these mice were activated by both CT26.WT-hHER2 and CT26.WT-mock cells. In the mouse model, DS-8201a treatment raised a population of intratumoral DCs (CD45+CD11c+MHC class II+) and increased DC expression of CD86, a DC activation marker; DXd also up-regulated CD86 expression on BMDCs in vitro. Furthermore, DS-8201a up-regulated PD-L1 and MHC class I expression on tumor cells. Notably, antitumor effects of the combination of DS-8201a with an anti-PD-1 antibody were better than those of monotherapy. Conclusions: DS-8201a elicits immune responses via mechanisms other than cytotoxic effects on tumor cells. This finding suggests additional benefits of combining DS-8201a with an immune checkpoint inhibitor (ICI). The combination of DS-8201a and an anti-PD-1 antibody was effective in tumor suppression, indicating that DS-8201a may be successfully combined with an ICI in human clinical applications.

scholarly journals Hypoxia augments MHC class I antigen presentation via facilitation of ERO1-α-mediated oxidative folding in murine tumor cells

2016 ◽  
Vol 46 (12) ◽  
pp. 2842-2851 ◽  
Author(s):  
Toshimitsu Kajiwara ◽  
Tsutomu Tanaka ◽  
Kazuharu Kukita ◽  
Goro Kutomi ◽  
Keita Saito ◽  
...  
Keyword(s):  
Antigen Presentation ◽  
Tumor Cells ◽  
Mhc Class I ◽  
Class I ◽  
Oxidative Folding ◽  
Murine Tumor ◽  
Mhc Class I Antigen ◽  
Murine Tumor Cells
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