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Q-fever is a flu-like illness caused by Coxiella burnetii (Cb), a highly infectious intracellular bacterium. There is an unmet need for a safe and effective vaccine for Q-fever. Correlates of immune protection to Cb infection are limited. We proposed that analysis by longitudinal high dimensional immune (HDI) profiling using mass cytometry combined with other measures of vaccination and protection could be used to identify novel correlates of effective vaccination and control of Cb infection. Using a vaccine-challenge model in HLA-DR transgenic mice, we demonstrated significant alterations in circulating T-cell and innate immune populations that distinguished vaccinated from naïve mice within 10 days, and persisted until at least 35 days post-vaccination. Following challenge, vaccinated mice exhibited reduced bacterial burden and splenomegaly, along with distinct effector T-cell and monocyte profiles. Correlation of HDI data to serological and pathological measurements was performed. Our data indicate a Th1-biased response to Cb, consistent with previous reports, and identify Ly6C, CD73, and T-bet expression in T-cell, NK-cell, and monocytic populations as distinguishing features between vaccinated and naïve mice. This study refines the understanding of the integrated immune response to Cb vaccine and challenge, which can inform the assessment of candidate vaccines for Cb.

Exogenously applied mature naive B220+ /CD19+ /IgM+ /IgD+ B cells are strongly protective in the context of tissue injury. However, the mechanisms by which B cells detect tissue injury and aid repair remain elusive. Here, we show in distinct models of skin and brain injury that MyD88-dependent toll-like receptor (TLR) signaling through TLR2/6 and TLR4 is essential for the protective benefit of B cells in vivo, while B cell-specific deletion of MyD88 abrogated this effect. The B cell response to injury was multi-modal with simultaneous production of both regulatory cytokines, such as IL-10, IL-35, and transforming growth factor beta (TGFβ), and inflammatory cytokines, such as tumor necrosis factor alpha (TNFα), IL-6, and interferon gamma. Cytometry analysis showed that this response was time and environment-dependent in vivo, with 20%-30% of applied B cells adopting an immune modulatory phenotype with high co-expression of anti- and pro-inflammatory cytokines after 18-48 h at the injury site. B cell treatment reduced the expression of TNFα and increased IL-10 and TGFβ in infiltrating immune cells and fibroblasts at the injury site. Proteomic analysis further showed that B cells have a complex time-dependent homeostatic effect on the injured microenvironment, reducing the expression of inflammation-associated proteins, and increasing proteins associated with proliferation, tissue remodeling, and protection from oxidative stress. These findings chart and validate a first mechanistic understanding of the effects of B cells as an immunomodulatory cell therapy in the context of tissue injury.

For the zoonotic disease Q fever, serological analysis plays a dominant role in the diagnosis ofCoxiella burnetiiinfection and in pre-screening for past exposure prior to vaccination. A number of studies suggest that assessment ofC. burnetii-specific T-cell IFNγ responses may be a more sensitive tool to assess past exposure. In this study, we assessed the performance of a whole bloodC. burnetiiIFNγ release assay in comparison to serological detection in an area of high Q fever incidence in 2014, up to seven years after initial exposure during the Dutch Q fever outbreak 2007-2010. In a cohort of >1500 individuals from the Dutch outbreak village of Herpen, approximately 60% had mounted IFNγ responses toC. burnetii. This proportion was independent of theCoxiellastrain used for stimulation and much higher than the proportion of individuals scored sero-positive using the serological gold standard immunofluorescence assay. Moreover,C. burnetii-specific IFNγ responses were found to be more durable than antibody responses in two sub-groups of individuals known to have sero-converted as of 2007 or previously reported to the municipality as notified Q fever cases. A novel ready-to-use version of the IFNγ release assay assessed in a subgroup of pre-exposed individuals in 2021 (10-14 years post exposure) proved again to be more sensitive than serology in detecting past exposure. These data demonstrate thatC. burnetii-induced IFNγ release is indeed a more sensitive and durable marker of exposure toC. burnetiithan are serological responses. In combination with a simplified assay version suitable for implementation in routine diagnostic settings, this makes the assessment of IFNγ responses a valuable tool for exposure screening to obtain epidemiological data, and to identify previously exposed individuals in pre-vaccination screens.

Infection with Coxiella burnetii, the causative agent of Q fever, can result in life-threatening persistent infection. Reactogenicity hinders worldwide implementation of the only licensed human Q fever vaccine. We previously demonstrated long-lived immunoreactivity in individuals with past symptomatic and asymptomatic Coxiella infection (convalescents) to promiscuous HLA-class II C. burnetii epitopes, providing the basis for a novel T-cell-targeted subunit vaccine. Here we investigated in a cohort of 22 individuals with persistent infection (chronic Q fever) whether they recognize the same set of epitopes, or distinct epitopes that could be candidates for a therapeutic vaccine or aid in the diagnosis of persistent infection.Individuals with chronic Q fever showed strong class II epitope-specific cultured ELISpot responses largely overlapping with the peptide repertoire identified previously for convalescents. Five additional peptides were recognized more frequently by chronic subjects, but there was no combination of epitopes uniquely recognized by or non-reactive in chronic Q fever subjects. Consistent with more recent/prolonged exposure, we found, however, stronger direct ex vivo responses to whole-cell C. burnetii and individual peptides in direct ELISpot than in convalescents.In conclusion, we have validated and expanded a previously published set candidate epitopes for a novel T-cell targeted subunit Q fever vaccine in the context of chronic Q fever patients and demonstrated that they successfully mounted a T-cell response comparable to that of convalescents. Finally, we demonstrate that individuals treated for chronic Q fever mount a broader ex vivo response to class II epitopes than convalescents, which could be explored for diagnostic purposes.

Supplemental Digital Content is available in the text., Background. We previously demonstrated that the incorporation of the chemokine CXCL12 into alginate microbeads supported long-term survival of microencapsulated auto-, allo-, and xenogeneic islets in murine models of diabetes without systemic immune suppression. The purpose of this study was to test whether CXCL12 could abrogate foreign body responses (FBRs) against alginate microbeads which were empty or contained autologous islets in healthy nonhuman primates (NHPs; n = 4). Methods. Two NHPs received intraperitoneal implants of 400 000 alginate microbeads with or without CXCL12, and postimplantation immunological and histopathological changes were evaluated up to 6 months postimplantation. A similar evaluation of autologous islets in CXCL12-containing alginate microbeads was performed in NHPs (n = 2). Results. CXCL12-containing alginate microbeads were associated with a markedly reduced FBR to microbeads. Host responses to microbead implants were minimal, as assessed by clinical observations, blood counts, and chemistry. Evaluation of encapsulated islets was limited by the development of necrotizing pancreatitis after hemipancreatectomy in 1 NHP. A limited number of functioning islets were detectable at 6 months posttransplantation in the second NHP. In general, empty microbeads or islet-containing beads were found to be evenly distributed through the intraperitoneal cavity and did not accumulate in the Pouch of Douglas. Conclusions. Inclusion of CXCL12 in alginate microbeads minimized localized FBR. The NHP autologous islet implant model had limited utility for excluding inflammatory/immune responses to implanted islets because of the complexity of pancreatic surgery (hemipancreatectomy) before transplantation and the need to microencapsulate and transplant encapsulated autologous islets immediately after pancreatectomy and islet isolation.

The treatment of skin with a low-power continuous-wave (CW) near-infrared (NIR) laser prior to vaccination is an emerging strategy to augment the immune response to intradermal vaccine, potentially substituting for chemical adjuvant, which has been linked to adverse effects of vaccines. This approach proved to be low cost, simple, small, and readily translatable compared with the previously explored pulsed-wave medical lasers. However, little is known on the mode of laser–tissue interaction eliciting the adjuvant effect. In this study, we sought to identify the pathways leading to the immunological events by examining the alteration of responses resulting from genetic ablation of innate subsets including mast cells and specific dendritic cell populations in an established model of intradermal vaccination and analyzing functional changes of skin microcirculation upon the CW NIR laser treatment in mice. We found that a CW NIR laser transiently stimulates mast cells via generation of reactive oxygen species, establishes an immunostimulatory milieu in the exposed tissue, and provides migration cues for dermal CD103+ dendritic cells without inducing prolonged inflammation, ultimately augmenting the adaptive immune response. These results indicate that use of an NIR laser with distinct wavelength and power is a safe and effective tool to reproducibly modulate innate programs in skin. These mechanistic findings would accelerate the clinical translation of this technology and warrant further explorations into the broader application of NIR lasers to the treatment of immune-related skin diseases.

Beta cell replacement has the potential to restore euglycemia in patients with insulin dependent diabetes. While great progress has been made in establishing allogeneic islet transplantation from deceased donors as the standard of care for those with the most labile diabetes, it is also clear that the deceased donor organ supply cannot possibly treat all those who could benefit from restoration of a normal beta cell mass, especially if immunosuppression were not required. Against this background, the International Pancreas and Islet Transplant Association (IPITA) in collaboration with the Harvard Stem Cell Institute (HSCI), the Juvenile Diabetes Research Foundation (JDRF), and the Helmsley Foundation held a 2-day Key Opinion Leaders Meeting in Boston in 2016 to bring together experts in generating and transplanting beta cells derived from stem cells. The following summary highlights current technology, recent significant breakthroughs, unmet needs and roadblocks to stem-cell-derived beta cell therapies, with the aim of spurring future preclinical collaborative investigations and progress toward the clinical application of stem cell-derived beta cells.

Background Chemotherapy initially reduces the tumor burden in patients with ovarian cancer. However, tumors recur in over 70% of patients, creating the need for novel therapeutic approaches. Methods We evaluated Ruxolitinib, an FDA-approved JAK 1/2 kinase inhibitor, as a potential adjunctive therapy for use with low-dose Taxol (Paclitaxel) by assessing the impact on in vitro proliferation and colony formation of ID8 cells or human TOV-112D ovarian cancer cells, as well as flow cytometric measurement of surface markers associated with cellular stress and stemness by ID8 cells. The syngeneic ID8 murine model of ovarian cancer was used to assess the impact of Ruxolitinib and Taxol, individually and in combination, on tumor initiation and growth, as well as capacity to extend survival. Results Ruxolitinib (≤10 μM) sensitized both ID8 and TOV-112D cells to low concentrations of Taxol (≤5 nM), limiting cell proliferation and colony formation in vitro. Mechanistically, we demonstrated that Taxol induced expression of stress and stemness markers including GRP78 and CD133 was significantly reduced by addition of Ruxolitinib. Finally, we demonstrated that a single administration of a low-dose of Taxol (10 mg/Kg) together with daily Ruxolitinib (30 mg/Kg; which is equivalent to plasma concentrations of ∼ 0.01 μM steady-state) limited ID8 tumor growth in vivo and significantly extended median survival up to 53.5% (median 70 v 107.5 days) as compared to control mice. Conclusion Together, these data support the use of Ruxolitinib in combination with low-dose Taxol as a therapeutic approach with the potential for improved efficacy and reduced side effects for patients with recurrent ovarian cancer.

Background Although dendritic cell (DC) vaccines are considered to be promising treatments for advanced cancer, their production and administration is costly and labor-intensive. We developed a novel immunotherapeutic agent that links a single-chain antibody variable fragment (scFv) targeting mesothelin (MSLN), which is overexpressed on ovarian cancer and mesothelioma cells, to Mycobacterium tuberculosis (MTB) heat shock protein 70 (Hsp70), which is a potent immune activator that stimulates monocytes and DCs, enhances DC aggregation and maturation and improves cross-priming of T cells mediated by DCs. Methods Binding of this fusion protein with MSLN on the surface of tumor cells was measured by flow cytometry and fluorescence microscopy. The therapeutic efficacy of this fusion protein was evaluated in syngeneic and orthotopic mouse models of papillary ovarian cancer and malignant mesothelioma. Mice received 4 intraperitoneal (i.p.) treatments with experimental or control proteins post i.p. injection of tumor cells. Ascites-free and overall survival time was measured. For the investigation of anti-tumor T-cell responses, a time-matched study was performed. Splenocytes were stimulated with peptides, and IFNγ- or Granzyme B- generating CD3+CD8+ T cells were detected by flow cytometry. To examine the role of CD8+ T cells in the antitumor effect, we performed in vivo CD8+ cell depletion. We further determined if the fusion protein increases DC maturation and improves antigen presentation as well as cross-presentation by DCs. Results We demonstrated in vitro that the scFvMTBHsp70 fusion protein bound to the tumor cells used in this study through the interaction of scFv with MSLN on the surface of these cells, and induced maturation of bone marrow-derived DCs. Use of this bifunctional fusion protein in both mouse models significantly enhanced survival and slowed tumor growth while augmenting tumor-specific CD8+ T-cell dependent immune responses. We also demonstrated in vitro and in vivo that the fusion protein enhanced antigen presentation and cross-presentation by targeting tumor antigens towards DCs. Conclusions This new cancer immunotherapy has the potential to be cost-effective and broadly applicable to tumors that overexpress mesothelin.

Safe and effective immunologic adjuvants are often essential for vaccines. However, the choice of adjuvant for licensed vaccines is limited, especially for those that are administered intradermally. We show that non-tissue damaging, near-infrared (NIR) laser light given in short exposures to small areas of skin, without the use of additional chemical or biological agents, significantly increases immune responses to intradermal influenza vaccination without augmenting IgE. The NIR laser-adjuvanted vaccine confers increased protection in a murine influenza lethal challenge model as compared to unadjuvanted vaccine. We show that NIR laser treatment induces the expression of specific chemokines in the skin resulting in recruitment and activation of dendritic cells and is safe to use in both mice and humans. The NIR laser adjuvant technology provides a novel, safe, low-cost, simple-to-use, potentially broadly applicable and clinically feasible approach to enhancing vaccine efficacy as an alternative to chemical and biological adjuvants.

The recent approval of a prostate cancer vaccine has renewed hope for anticancer immunotherapies. However, the immunosuppressive tumor microenvironment may limit the effectiveness of current immunotherapies. Antiangiogenic agents have the potential to modulate the tumor microenvironment and improve immunotherapy, but they often are used at high doses in the clinic to prune tumor vessels and paradoxically may compromise various therapies. Here, we demonstrate that targeting tumor vasculature with lower vascular-normalizing doses, but not high antivascular/antiangiogenic doses, of an anti-VEGF receptor 2 (VEGFR2) antibody results in a more homogeneous distribution of functional tumor vessels. Furthermore, lower doses are superior to the high doses in polarizing tumor-associated macrophages from an immune inhibitory M2-like phenotype toward an immune stimulatory M1-like phenotype and in facilitating CD4 + and CD8 + T-cell tumor infiltration. Based on this mechanism, scheduling lower-dose anti-VEGFR2 therapy with T-cell activation induced by a whole cancer cell vaccine therapy enhanced anticancer efficacy in a CD8 + T-cell–dependent manner in both immune-tolerant and immunogenic murine breast cancer models. These findings indicate that vascular-normalizing lower doses of anti-VEGFR2 antibody can reprogram the tumor microenvironment away from immunosuppression toward potentiation of cancer vaccine therapies. Given that the combinations of high doses of bevacizumab with chemotherapy have not improved overall survival of breast cancer patients, our study suggests a strategy to use antiangiogenic agents in breast cancer more effectively with active immunotherapy and potentially other anticancer therapies.

Vaccinating immunocompromised patients for common infectious diseases, including influenza, is a commonly missed opportunity. Clinicians caring for immunocompromised individuals often focus on other more immediate health concerns, or may believe that vaccines do not provide worthwhile protection or could even be harmful. In a recent series of 112 oncology patients at a single center in France, only 34 (30%) had undergone vaccination against influenza in the past year [1]. Numerous studies have shown reasonable rates of seroprotection and seroconversion in a variety of immunocompromised hosts, including oncology patients, with very minimal downside. Therefore, seasonal flu vaccination is broadly recommended across immunocompromised patient populations [2–4]. Bogoch et al. [5] demonstrated that the recent H1N1 influenza pandemic caused severe illness in a cohort of immunocompromised solid organ and bone marrow transplant patients from our hospitals. The hospitalization rate in this transplant setting was 71%, which far exceeded the hospitalization rate among confirmed cases in the general population, generally

Background HIV-1 is a pathogen that T cell responses fail to control. HIV-1gp120 is the surface viral envelope glycoprotein that interacts with CD4 T cells and mediates entry. HIV-1gp120 has been implicated in immune dysregulatory functions that may limit anti-HIV antigen-specific T cell responses. We hypothesized that in the context of early SHIV infection, immune dysregulation of antigen-specific T-effector cell and regulatory functions would be detectable and that these would be associated or correlated with measurable concentrations of HIV-1gp120 in lymphoid tissues. Methods Rhesus macaques were intravaginally inoculated with a Clade C CCR5-tropic simian-human immunodeficiency virus, SHIV-1157ipd3N4. HIV-1gp120 levels, antigen-specificity, levels of apoptosis/anergy and frequency and function of Tregs were examined in lymph node and blood derived T cells at 5 and 12 weeks post inoculation. Results/Conclusions We observed reduced responses to Gag in CD4 and gp120 in CD8 lymph node-derived T cells compared to the peripheral blood at 5 weeks post-inoculation. Reduced antigen-specific responses were associated with higher levels of PD-1 on lymph node-derived CD4 T cells as compared to peripheral blood and uninfected lymph node-derived CD4 T cells. Lymph nodes contained increased numbers of Tregs as compared to peripheral blood, which positively correlated with gp120 levels; T regulatory cell depletion restored CD8 T cell responses to Gag but not to gp120. HIV gp120 was also able to induce T regulatory cell chemotaxis in a dose-dependent, CCR5-mediated manner. These studies contribute to our broader understanding of the ways in which HIV-1 dysregulates T cell function and localization during early infection.

The chemokine CXCL12 and its receptor CXCR4 are expressed widely in human cancers, including ovarian cancer, in which they are associated with disease progression at the levels of tumor cell proliferation, invasion, and angiogenesis. Here, we used an immunocompetent mouse model of intraperitoneal papillary epithelial ovarian cancer to show that modulation of the CXCL12/CXCR4 axis in ovarian cancer has multimodal effects on tumor pathogenesis associated with induction of antitumor immunity. siRNA-mediated knockdown of CXCL12 in BR5-1 cells that constitutively express CXCL12 and CXCR4 reduced cell proliferation in vitro, and tumor growth in vivo. Similarly, treatment of BR5-1–derived tumors with AMD3100, a selective CXCR4 antagonist, resulted in increased tumor apoptosis and necrosis, reduction in intraperitoneal dissemination, and selective reduction of intratumoral FoxP3+ regulatory T cells (Treg). Compared with controls, CXCR4 blockade greatly increased T-cell–mediated antitumor immune responses, conferring a significant survival advantage to AMD3100-treated mice. In addition, the selective effect of CXCR4 antagonism on intratumoral Tregs was associated with both higher CXCR4 expression and increased chemotactic responses to CXCL12, a finding that was also confirmed in a melanoma model. Together, our findings reinforce the concept of a critical role for the CXCL12/CXCR4 axis in ovarian cancer pathogenesis, and they offer a definitive preclinical validation of CXCR4 as a therapeutic target in this disease. Cancer Res; 71(16); 5522–34. ©2011 AACR.

Chemoattraction and chemorepulsion are complex directional responses of a cell to external chemotactic stimuli. The decision of a cell to move towards or away from a chemokinetic source includes detection and quantitation of the gradient of the chemotactic agent, biochemical transmission of the stimulus, and translation into a directional migration. This chapter describes a number of in vitro and in vivo assays that can be used to generate and measure both chemoattraction and chemorepulsion of leucocytes. These tools may eventually allow the further characterisation of the mechanism of this complex and physiologically and pathologically important phenomenon.

The thymic microenvironment provides essential support for the generation of a functional and diverse population of human T cells. In particular, the three-dimensional (3D) thymic architecture contributes to critical cell-cell interactions. We report that thymic stroma, arrayed on a synthetic 3D matrix, supports the development of functional human T cells from hematopoietic precursor cells. Newly generated T cells contain T-cell receptor excision circles and are both fully mature and functional. The coculture of T-cell progenitors with thymic stroma can thus be used to generate de novo functional and diverse T-cell populations. This novel tissue engineered thymic system has biological applications for the study of T-lymphopoiesis and self-tolerance as well as potential therapeutic applications including the immune reconstitution of immunocompromised patients and the induction of tolerance in individuals receiving tissue or organ transplants.

Most antigenic tumors are able to evade the immune system despite T cell recognition of tumor specific antigens. The chemokine, stromal derived factor- 1 (SDF-1 or CXCL12) is constitutively expressed by both normal and neoplastic tissues and is involved in tumor growth, metastasis and modulation of the anti-tumor immune response. We have previously shown that human T cells are repelled by the chemokine SDF-1, in a concentration-dependent and CXCR4 receptor-mediated manner. We proposed that the repulsion of tumor-specific T cells from a tumor expressing SDF-1 may represent a novel mechanism of immune evasion. B16 melanoma cells stably expressing OVA were genetically modified to constitutively express SDF-1 using a bicistronic MSCV2.2 retroviral transfer vector encoding murine SDF-1α and EGFP. SDF-1 generated by transduced cells was 58 ± 28.5 ng/ml/1x106 cells/24 hours as measured by ELISA. Immunization of mice with irradiated B16/OVA cells lead to destruction of B16/OVA.MSCV control tumors but not tumors expressing high levels of SDF-1 (p=0.0001). Failure to reject B16/OVA.SDF-1 tumors was associated with a reduction of T cell infiltration compared to control B16/OVA.MSCV (p=0.001). Similarly, early recruitment of adoptively-transferred OVA-specific CD8+ T cells into B16/OVA.SDF-1 tumors was significantly reduced in comparison to B16/OVA.MSCV control tumors as demonstrated by immunohistochemistry and real-time magnetic resonance imaging of nanoparticle labeled CTLs (p=0.018). Transferred memory OVA-specific CD8+ T-cells demonstrated antitumor activity against B16/OVA.MSCV control tumors but not against B16/OVA-SDF-1 tumors (p=0.04). Isolation and FACS analysis of tumor-infiltrating lymphocytes showed a 4-fold reduction of T cells in B16/OVA.SDF-1 compared to B16/OVA.MSCV control tumors (p=0.005). The in-vitro killing activity of tumor specific CD8+ T cells against B16/OVA.SDF-1 tumors was significantly reduced compared to B16/OVA.MSCV control tumors when measured in 51Cr release assay performed in a flat-bottom well system where cytotoxicity was dependent on effector cell migration (p=0.0004). Preincubation of OT-I CD8+ T cells with the CXCR4 antagonist AMD3100 restored their cytolytic activity against B16/OVA.SDF-1 cells (p=0.045). These data support the thesis that the active movement of tumor-specific T cells away from SDF-1, termed fugetaxis, may provide a novel mechanism by which a tumor evades challenge by immune effector cells and raises the possibility of the development of a novel immunotherapeutic approach to cancer.

Human immunodeficiency virus type 1 (HIV-1) proviruses containing deletions between nucleotides 301 and 319 express viral proteins but exhibit marked attenuation in the packaging of viral RNA into virions (A. Lever, H. Gottlinger, W. Haseltine, and J. Sodroski, J. Virol. 63:4085-4087, 1989; A. Aldovini and R. A. Young, J. Virol. 64:1920-1926, 1990). Here we report that such packaging-defective proviruses can provide trans-acting viral elements required for the transfer of a HIV-1 vector to Jurkat human lymphocytes. The transferred vector was unable to encode HIV-1 genes, indicating that the long terminal repeats and the immediate flanking viral sequences are sufficient for packaging, reverse transcription, and integration. The generation of replication-competent viruses in this system was reduced to undetectable levels by providing the trans-acting viral functions on two separate expression plasmids. This defective retroviral vector provides a means of efficiently introducing desired genetic elements, in the absence of HIV-1 genes, into HIV-1 target cells.

ObjectivesIn view of evidence that mature cells play a role in modulating the stem cell niche and thereby stem cell potential and proliferation, we hypothesized that a mature bone marrow (BM) mononuclear cell (MNC) infusion subfraction may have particular potency in promoting hematopoietic or resident stem cell-induced cardiac repair post-infarction.BackgroundTreatment of acute myocardial infarction (MI) with BM MNC infusion has shown promise for improving patient outcomes. However, clinical data are conflicting, and demonstrate modest improvements. BM MNCs consist of different subpopulations including stem cells, progenitors, and differentiated leukocytes.MethodsStem cells (c-kit+) and subsets of mature cells including myeloid lineage, B and T-cells were isolated from bone marrow harvested from isogeneic donor rats. Recipient rats had baseline echocardiography then coronary artery ligation; 1 × 106 cells (enriched subpopulations or combinations of subpopulations of BM MNC) or saline was injected into ischemic and ischemic border zones. Cell subpopulations were either injected fresh or after overnight culture. After 2 weeks, animals underwent follow-up echocardiography. Cardiac tissue was assayed for cardiomyocyte proliferation and apoptosis.ResultsFractional ventricular diameter shortening was significantly improved compared with saline (38 ± 3.2%) when B cells alone were injected fresh (44 ± 3.0%, p = 0.035), or after overnight culture (51 ± 2.9%, p < 0.001), or after culture with c-kit+ cells (44 ± 2.4%, p = 0.062). B cells reduced apoptosis at 48 h after injection compared with control cells (5.7 ± 1.2% vs. 12.6 ± 2.0%, p = 0.005).ConclusionsIntramyocardial injection of B cells into early post-ischemic myocardium preserved cardiac function by cardiomyocyte salvage. Other BM MNC subtypes were either ineffective or suppressed cardioprotection conferred by an enriched B cell population.

Meeting abstracts Malignant tumors escape from host immune surveillance through multiple mechanisms. Of these, abnormal tumor vasculature and hypoxia are critical in establishing an immunosuppressive tumor microenvironment, and consequently, impeding an active cancer immunotherapy. Thus, we