murine leukemia cells
Serhan N, Mouchel PL, Medina P, Segala G, Mougel A, Saland E, Rives A, Lamaziere A, Despres G, Sarry JE, Larrue C, Vergez F, Largeaud L, Record M, Récher C, Silvente-Poirot S, Poirot M. Cancers (Basel). (A-D) The T-cell populations in the spleen were analyzed and identified as CD3+ expressing either CD8 or CD4. Depletion of endogenous tumor-associated regulatory T cells improves the efficacy of adoptive cytotoxic T-cell immunotherapy in murine acute myeloid leukemia. Dynamics and function of Langerhans cells in vivo: dermal dendritic cells colonize lymph node areas distinct from slower migrating Langerhans cells. Mice with established leukemia had a significantly increased percentage of CD4+FoxP3+ cells in both the liver and spleen (Figure 4A-B). When splenic CD11b+ cells were isolated 20 days after leukemia challenge and cultured with CFSE-labeled lymphocytes, the proliferation of CD4+ T cells was significantly reduced relative to cultures containing CD11b+ cells from control mice, suggesting greater suppressive activity on a per cell basis (Figure 4F). Get the latest research from NIH: https://www.nih.gov/coronavirus. Nonspecific Fc receptor binding was blocked with anti-CD16/32 clone 2.4G2 (prepared in-house). *P < .05; **P < .01; ***P < .001; ****P < .0001 (1-way ANOVA with a Bonferroni posttest). Together these data suggest that the capacity of the vaccine to stimulate NK T cells in established leukemia is largely intact. Acute Myeloid Leukemia Genetics: Risk Stratification and Implications for Therapy. These results indicate that Tregs are partially responsible for the inefficacy of therapeutic leukemia/α-GalCer vaccination. USA.gov. Papaemmanuil E., Gerstung M., Bullinger L., Gaidzik V.I., Paschka P., Roberts N.D., Potter N.E., Heuser M., Thol F., Bolli N., et al. 2002;8(12):3702-3709. (E) Kaplan-Meier plots showing symptom-free survival of mice vaccinated with leukemia/α-GalCer and challenged with C1498 at day zero. (C) *P < .05 (log-rank Mantel-Cox test). Front Cell Dev Biol. The retrovirus MuLV has a positive, single-stranded sense RNA that replicates via reverse transcription. Pitfalls of vaccinations with WT1-, Proteinase3- and MUC1-derived peptides in combination with MontanideISA51 and CpG7909. Enhancement of the anti-tumor efficacy of a GM-CSF-secreting tumor cell immunotherapy in preclinical models by cytosine arabinoside. Although this suppressive environment impaired both effector arms of the immune response, CD4+ T-cell responses were more severely affected. doi: 10.1038/nrc2091. ( A ) Spontaneous…, NLM © 2014 by The American Society of Hematology, Copyright ©2020 by American Society of Hematology, Document1. Autophagy and Stem Cells: Self-Eating for Self-Renewal.
2020 Feb 26;9(3):544. doi: 10.3390/cells9030544. USA.gov. It is possible therefore that the leukemic environment induces broad CD4+ T-cell dysfunction, perhaps including the inability to provide T-cell help to CD8+ T cells.
Quercetin decreased the weight of the spleen and liver compared with the olive oil treated animals. Statistical analysis compared therapeutic α-GalCer vaccination plus PC61 to therapeutic α-GalCer vaccination. Symptom-free survival was analyzed and is graphed. We next wanted to determine the effect of cytarabine pretreatment on the vaccine-induced response. Interactions between DCs and NKT cells promote CD40 signaling, leading to DC activation, which increases the capacity of DCs to stimulate peptide-specific T cells.23,24 Significantly, vaccines comprising irradiated tumor cells pulsed with α-GalCer have been shown to be effective in murine models of hematopoietic malignancies, including acute myeloid leukemia (AML) and acute lymphoid leukemia,23,27,28 and in other malignancies.25,27,29. Established leukemia disrupts leukemia/α-GalCer vaccine–mediated CD4+ T-cell function. Tan TW, Lin YT, Yang JS, Lu CC, Chiang JH, Wu CL, Lin JP, Tang NY, Yeh CC, Fan MJ, Chung JG. Wilms’ tumor protein 1 (WT1) peptide vaccination in AML patients: predominant TCR CDR3β sequence associated with remission in one patient is detectable in other vaccinated patients. 2020 May 11;39(1):85. doi: 10.1186/s13046-020-01580-4.
On day 23, 1 group of chemotherapy-treated mice was vaccinated with leukemia/α-GalCer, and responses were analyzed 1 week later. (C-E) Symbols represent treatments: unvaccinated (●), nonleukemic and nonvaccinated (◆), vaccinated with α-GalCer–pulsed irradiated leukemia cells (▪), vaccinated with unpulsed irradiated leukemia cells (□), vaccinated with free α-GalCer (△), depletion of CD4+ cells (▲), and depletion of CD8+ cells (▼). Please enable it to take advantage of the complete set of features! Here we investigated the efficacy of a vaccine comprising irradiated leukemia cells pulsed with α-GalCer in a murine acute leukemia model. -, Welch J., Ley T., Link D., Miller C. The origin and evolution of mutations in acute myeloid leukemia. Leuk Res. Murine T cells are metabolically impaired by AML cells invitro and invivo. (H-I) The expression of CD40 and CD86 on langerin+CD8α+ DCs, respectively. Antibody to Langerin/CD207 localizes large numbers of CD8alpha+ dendritic cells to the marginal zone of mouse spleen. Cancer-associated immunosuppression can present a significant barrier to effective vaccine-based immunotherapy.30 AML generates an immunosuppressive environment,31,32 characterized by impaired DC function33 and increased levels of regulatory T cells (Tregs).35-37 It follows that immunotherapy may be most effectively used during morphologic remission after induction chemotherapy. The murine leukemia viruses are group/type VI retroviruses belonging to the gammaretroviral genus of the Retroviridae family. Therefore, vaccination provided durable protection against leukemia when administered during remission following cytarabine chemotherapy, suggesting that an α-GalCer–pulsed irradiated leukemia cell vaccine may be a promising postremission immunotherapy for acute leukemia. Atg7-deficient LICs displayed enhanced mitochondrial activity and reactive oxygen species production together with increased cell death. Lab. Finally, cytarabine (AraC) treatment activated autophagy in LICs, and Atg7 deletion potentiated the therapeutic effects of AraC, which included decreased LICs and prolonged survival, suggesting that autophagy contributes to AraC resistance. To analyze whether the C1498 line itself had immunosuppressive capabilities, C1498 cells were cultured with CFSE-labeled lymphocytes, and T-cell proliferation was compared with cultures containing naïve CD11b+ splenocytes. (F-G) The splenic langerin+CD8α+ DC population in lang-EGFP mice was analyzed 24 hours after vaccination. (D) Flow cytometric identification of splenic CD11b+Ly6G+ MDSCs. FAQ
Nutritional immunology: function of natural killer cells and their modulation by resveratrol for cancer prevention and treatment. doi: 10.1038/35106108. Overall, these data indicate that there may be several immunosuppressive activities at play in the context of established leukemia. Hermetet F, Mshaik R, Simonet J, Callier P, Delva L, Quéré R. Sci Rep. 2020 Sep 30;10(1):16187. doi: 10.1038/s41598-020-73020-4. The ratio of CD44hi CD8+ effector T cells to CD4+FoxP3+ Tregs and ratio of CD44hi CD4+ effector (eff) T cells to CD4+FoxP3+ Tregs in (E,G) the spleen and (F,H) the liver, respectively. Cytarabine pretreatment does not suppress vaccine-induced immune responses. Mechanism of T cell tolerance induced by myeloid-derived suppressor cells. 2007;7:233–245. To determine the effector cells responsible for vaccine-induced protection against development of leukemia, mice were vaccinated and depleted of CD4+ or CD8+ cells 2 days before C1498 challenge to ensure that the depletion would not interfere with cells potentially important for immune priming. Myeloid leukemia C1498 as a screen for cancer chemotherapeutic agents. Acute myeloid leukemia creates an arginase-dependent immunosuppressive microenvironment. Systematic Analysis of Autophagy-Related Signature Uncovers Prognostic Predictor for Acute Myeloid Leukemia. (A) Flow cytometric identification of Tregs.
Together, these results indicate that the inefficacy of the vaccine was not attributed to a failure to activate NKT cells or DCs.
Haematologica. Acute myeloid leukaemia (AML) is a rare but severe form of human cancer that results from a limited number of functionally cooperating genetic abnormalities leading to uncontrolled proliferation and impaired differentiation of hematopoietic stem and progenitor cells. Dendritic cell function can be modulated through cooperative actions of TLR ligands and invariant NKT cells. HHS
Analysis was performed with Prism 5.0 software (GraphPad Software, Inc.); P values <.05 were considered significant. Extract of Hedyotis diffusa Willd influences murine leukemia WEHI-3 cells in vivo as well as promoting T- and B-cell proliferation in leukemic mice. Fig. Supernatant cytokine levels were measured by cytokine bead array (Biorad Laboratories, Inc, Auckland, New Zealand) following culture with 1 000 000 splenocytes and 10 000 bone marrow (BM)–derived DCs (BM-DCs) loaded with C1498 lysate for 4 hours. The percentage of (J) PD-1+CD8+ and (K) PD-1+CD4+ T cells in the BM.
Because we found little evidence to support a role for cytarabine in modulating proportions of Tregs and MDSCs, the efficacy against rechallenge we observe when cytarabine is combined with vaccination may simply reflect the capacity of this drug to drastically reduce the burden of leukemia cells and the preexisting immunity afforded by the vaccine before rechallenge. Race and ethnicity in decisions about unrelated hematopoietic stem cell donation. J Exp Clin Cancer Res. To establish whether leukemia suppressed effector T cells, the vaccine-induced T-cell response was examined. In leukemia-bearing mice, IFN-γ production by CD4+, but not CD8+ T cells, was impaired. Immunotherapeutic strategies for relapse control in acute myeloid leukemia. Activation of natural killer T cells by alpha-galactosylceramide rapidly induces the full maturation of dendritic cells in vivo and thereby acts as an adjuvant for combined CD4 and CD8 T cell immunity to a coadministered protein. However, given that some antitumor activity was seen in the absence of CD8+ T cells, other CD4+ T-cell functions must be involved, perhaps as effectors in their own right,66 or through interactions with other MHC class II–expressing cells. -, Rowley J.D. For further information on this cell line and other parameters, including different strains, vendors, implant type and location and/or standards of care, please contact Covance. There is an unmet need for effective postremission therapies for acute leukemia that have reduced toxicity and cost compared with allo-SCT. Lin JP, Yang JS, Lu CC, Chiang JH, Wu CL, Lin JJ, Lin HL, Yang MD, Liu KC, Chiu TH, Chung JG. When a specific chemokine receptor must be evaluated, HEK-293 T cells transfected transiently or stably with the receptor should be used. Vaccinated animals had an increased proportion of CD3+ T cells compared with unvaccinated mice that was unaffected by cytarabine (Figure 6I).
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