Biomedical subjects

Hiroaki Saito

Publications and source records attributed to Hiroaki Saito.

At least 19 recordsLinked to original sources

PubMed2007

Prognostic significance of RCAS1 expression in relation to the infiltration of dendritic cells and lymphocytes in patients with esophageal carcinoma.

RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) expression was determined in 107 esophageal carcinoma patients by immunohistochemical procedures and compared with tumor infiltrating lymphocyte (TIL) and dendritic cell (DC) infiltration to evaluate the effect of RCAS1 on immune responses in esophageal carcinoma. RCAS1 immunoreactivity was detected in 59 of 107 patients (55.1%). RCAS1 expression was significantly correlated with the depth of invasion, lymph node metastasis, and histologic stage. RCAS1 expression tended to be correlated with a lower TIL density in tumors with marked DC infiltration. The survival time for patients with RCAS1-negative tumors was significantly longer than that for patients with RCAS1-positive tumors. Especially, the prognosis was predicted by RCAS1 in cases with marked DC infiltration. Multivariate analysis revealed that RCAS1 expression was an independent prognostic factor. RCAS1 expression may play an important role in evading the immunological defense mechanisms in esophageal carcinoma.

Aged↗

PubMed2006

A TNF receptor loop peptide mimic blocks RANK ligand-induced signaling, bone resorption, and bone loss.

Activating receptor activator of NF-kappaB (RANK) and TNF receptor (TNFR) promote osteoclast differentiation. A critical ligand contact site on the TNFR is partly conserved in RANK. Surface plasmon resonance studies showed that a peptide (WP9QY) that mimics this TNFR contact site and inhibits TNF-alpha-induced activity bound to RANK ligand (RANKL). Changing a single residue predicted to play an important role in the interaction reduced the binding significantly. WP9QY, but not the altered control peptide, inhibited the RANKL-induced activation of RANK-dependent signaling in RAW 264.7 cells but had no effect on M-CSF-induced activation of some of the same signaling events. WP9QY but not the control peptide also prevented RANKL-induced bone resorption and osteoclastogenesis, even when TNFRs were absent or blocked. In vivo, where both RANKL and TNF-alpha promote osteoclastogenesis, osteoclast activity, and bone loss, WP9QY prevented the increased osteoclastogenesis and bone loss induced in mice by ovariectomy or low dietary calcium, in the latter case in both wild-type and TNFR double-knockout mice. These results suggest that a peptide that mimics a TNFR ligand contact site blocks bone resorption by interfering with recruitment and activation of osteoclasts by both RANKL and TNF.

Amino Acid Sequence↗

PubMed2006

Expression of polo-like kinase 1 (PLK1) protein predicts the survival of patients with gastric carcinoma.

OBJECTIVE: To assess the prognostic value of polo-like kinase 1 (PLK1), an important regulator of cell cycle progression, in patients with gastric carcinoma. METHODS: PLK1 expression was determined in 160 gastric carcinoma patients by immunohistochemistry and compared with p53 expression and the proliferating cell nuclear antigen-labeling index (PCNA-LI) to evaluate the effect of PLK1 on tumor progression. Furthermore, PLK mRNA expression was determined in 26 advanced gastric cancer patients by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: PLK mRNA expression was detected in 25 (96.2%) patients by RT-PCR. Immunohistochemical staining revealed PLK1 expression in 84 (52.5%) patients. There were no significant relationships between PLK1 expression and various clinicopathological factors. PLK1 expression was significantly correlated with the PCNA-LI, but not p53 expression. The prognosis of patients with PLK1-positive tumors was significantly worse than that of patients with PLK1-negative tumors (p < 0.05). Moreover, multivariate analysis revealed that PLK1 expression was an independent prognostic factor. Patients with PLK1-positive and high PCNA-LI tumors showed a significantly poorer prognosis than patients with PLK1-negative and/or low PCNA-LI tumors. Furthermore, the prognosis of patients with PLK1- and p53-positive tumors was significantly worse than that of patients with PLK1- and p53-negative or PLK1-negative and p53-positive tumors. CONCLUSION: PLK1 expression may be a critical indicator of a poor prognosis in patients with gastric carcinoma.

Biomarkers, Tumor↗

PubMed2006

Interleukin-10 expression significantly correlates with minor CD8+ T-cell infiltration and high microvessel density in patients with gastric cancer.

We aimed to investigate the relationships between interleukin-10 (IL-10) expression and both the clinicopathological findings and prognoses in patients with gastric cancer and to compare IL-10 expression with microvessel (MV) density and CD8+ T lymphocyte infiltration to evaluate its effects on angiogenesis and immune responses in gastric cancer. IL-10 expression was determined in gastric cancer patients by reverse transcription-polymerase chain reaction (RT-PCR) or immunohistochemical procedures. Two of 7 normal gastric tissues showed IL-10 mRNA expression, while its expressions were confirmed in all advanced gastric carcinoma tissues examined (n=11) by RT-PCR. Immunohistochemical staining demonstrated that IL-10 expression was detected in 52 (47.7%) of 109 cases. There was a close correlation between IL-10 expression and MV density. IL-10 expression inversely correlated with CD8+ T-lymphocyte infiltration. The prognoses of patients whose tumors expressed IL-10 were significantly worse than those of patients whose tumors did not express IL-10. Multivariate analysis indicated IL-10 expression was an independent prognostic factor. IL-10 might be associated with tumor progression by stimulating angiogenesis and suppressing immune responses in gastric cancer.

Adenocarcinoma↗

PubMed2006

Distinct recurrence pattern and outcome of adenocarcinoma of the gastric cardia in comparison with carcinoma of other regions of the stomach.

BACKGROUND: Carcinoma arising in the cardioesophageal junction is a distinct clinical entity compared with tumors located in other regions of the stomach. The prognosis for adenocarcinoma of the upper stomach is considered to be relatively poorer than carcinomas of the more distal stomach. We have therefore investigated patients with carcinoma of the gastric cardia in order to evaluate the underlying cause of this poor prognosis. MATERIALS AND METHODS: Clinicopathologic features and postoperative prognosis of 101 patients with carcinoma of the cardia were evaluated and compared with findings on 1884 patients with tumors in other regions of the stomach. RESULTS: Tumors of the cardia had a mean size of 6.8 cm, which was significantly larger than the mean size of 5.9 cm for tumors found in the middle- and lower third of the stomach. The incidence of serosal invasion, lymph node metastasis, and lymphatic and blood vessel invasion was higher in association with adenocarcinoma of the cardia than with adenocarcinoma in remaining parts of the stomach. In the analysis of patients who had undergone curative resection, the 5-year survival rates were 61.6, 79.1, and 82.6% in patients with carcinoma of the cardia, upper one-third, and remaining middle- and lower one-third of the stomach, respectively, and the differences were statistically significant. Multivariate analysis indicated that adenocarcinoma of the gastric cardia is an independent prognostic factor. With regard to the site of recurrence, both lymph node and hematogenous recurrence were observed more frequently in the cardia than in the remaining parts of the stomach. CONCLUSIONS: Our data indicate that the prognosis of patients with adenocarcinoma of the gastric cardia is extremely poor. To improve their prognosis, new treatments in addition to gastrectomy with extensive lymph node dissection are needed.

Adenocarcinoma↗

PubMed2006

Docosahexaenoic acid levels in the lipids of spotted mackerel Scomber australasicus.

The lipid and FA compositions of various organs and of the stomach contents of Scomber australasicus were analyzed. DHA was characteristically the major FA of all the major lipid classes of all organs except for liver TAG. The mean DHA contents of the various organs accounted for more than 17% of the total FA (TFA), whereas those in the stomach contents, originating from the prey, fluctuated and were generally low. In particular, the DHA levels in the TAG from all organs of S. australasicus accounted for up to 17% of TFA, even though it is a neutral depot lipid. S. australasicus contained markedly high levels of DHA, even though it is a small-sized Scombridae species, and its high levels of DHA were close to those in large-sized highly migratory tuna species. Furthermore, DHA levels in its muscle TAG were consistently high, compared with those in the visceral TAG, which might be directly influenced by the prey lipids. These phenomena suggest that long-distance migration has a close relationship with high accumulation of DHA in fish tissues, since S. australasicus is reported to migrate in offshore water, similar to highly migratory tuna species. Additionally, the physiological selective accumulation of DHA in the muscle during migration is caused by in vivo metabolism of FA in the vascular system, suggesting that DHA is poorly used as a source of migration energy, though it is provided abundantly through the prey lipids.

Animal Migration↗

PubMed2006

Year-round high arachidonic acid levels in herbivorous rabbit fish Siganus fuscescens tissues.

To identify a stable resource of 20:4 n-6 (arachidonic acid, AA) in marine fish tissues, the lipid profiles of Siganus fuscescens organs (muscle, liver, and other viscera) and stomach contents were examined throughout the year. Crude total lipid (TL) contents in respective organs showed seasonal variations and were high in winter and low in summer. The main FA in TL were 16:0, 18:0, 16:1n-7, 18:1n-9, AA, and 22:6n-3 (DHA). These FA were those generally observed in marine fish lipids, except for comparatively high levels of AA. In TL of muscle and liver, AA showed relatively high values during the period from late May to August (muscle, 4.6-13.1%; liver, 4.5-9.1%), compared with other seasons (muscle, 4.3-9.5%; liver, 3.6-8.4%). The AA levels in TL of other viscera and stomach contents fluctuated (other viscera, 2.0-10.7%; stomach contents, 7.6-26.7%). Regardless of the fishing season, each organ contained a higher level of AA in polar lipids (PL) than in neutral lipids. It was concluded that the fish contain comparatively high levels of AA in their TL throughout the year, and they accumulate AA characteristically in their tissue PL, probably from dietary food sources. Moreover, it was suggested that S. fuscescens has potential utility as a natural marine source of nutritional lipids, because the fish contain comparatively high levels of DHA and AA.

Analysis of Variance↗

PubMed2006

Macroscopic tumor size as a simple prognostic indicator in patients with gastric cancer.

BACKGROUND: In some cancers, such as breast and lung, tumor size is included in the classification of disease stage. However, it's clinical significance remains elusive in gastric cancer. METHODS: To investigate the prognostic significance of macroscopic tumor size, we reviewed 1473 gastric cancer patients who underwent curative gastrectomy. RESULTS: An appropriate threshold of tumor size affecting patient survival was 8 cm. Patients were divided into 2 groups as follows: small size group (SSG=tumor size<8 cm) and large size group (LSG=tumor size>or=8 cm). LSG tumors were frequently observed in patients with undifferentiated types and with lymphatic and venous invasion. Moreover, tumor size was significantly related to depth of invasion and lymph node metastasis. The prognosis of LSG patients was significantly worse than that of SSG patients. Multivariate analysis showed that tumor size was an independent prognostic factor along with depth of invasion, lymph node metastasis, and lymphatic invasion. Recurrence patterns differed between the 2 groups. Peritoneal recurrence was observed in LSG more frequently than SSG patients (P<.001), whereas hematogenous recurrence was observed in SSG more frequently than in LSG patients (P<.05). The survival rates of patient with stages II-, IIIa-, and IIIb-LSG disease were almost the same as those with stages IIIa-, IIIb-, and IV-SSG disease, respectively. COMMENTS: Tumor size serves as a simple predictor of survival in patients with gastric cancer.

Adenocarcinoma↗

PubMed2006

Dendritic cell-based vaccination against cancer.

Vaccination against infectious agents represents a success of immunology, although many infectious diseases still evade the immune system, including chronic infections, such as tuberculosis, malaria, and HIV. Further progress is expected through rational design based on increased understanding of how the immune system works, and how the induction of protective immunity is regulated. The same principle applies to cancer vaccines, particularly because cancer is a chronic disease. Owing to their capacity to regulate cellular and humoral immunity, dendritic cells are increasingly used as vaccines; the immunogenicity of antigens delivered on dendritic cells has been shown in cancer patients. A better understanding of how dendritic cells regulate immune responses would allow clinicians to exploit them better to induce effective immunity against cancer.

Antigen Presentation↗

PubMed2006

Hydroxylated gedunin derivatives from Cedrela sinensis.

Four new limonoids, 11alpha-hydroxygedunin (1), 11beta-hydroxygedunin (2), 7-deacetoxy-7alpha,11alpha-dihydroxygedunin (3), and 7-deacetoxy-7alpha,11beta-dihydroxygedunin (4), were isolated from the cortex of Cedrela sinensis, together with three known compounds, gedunin (5), 7-deacetoxy-7alpha-hydroxygedunin (6), and 11-oxogedunin (7). The structures of 1-4 were determined by a combination of 2D NMR experiments and chemical methods and by X-ray crystallography of 1 and 2.

Animals↗

PubMed2006

Immunization with 3-oxododecanoyl-L-homoserine lactone-protein conjugate protects mice from lethal Pseudomonas aeruginosa lung infection.

Quorum-sensing systems have been reported to play a critical role in the pathogenesis of several bacterial infections. Recent data have demonstrated that Pseudomonas N-3-oxododecanoyl-L-homoserine lactone (3-oxo-C12-homoserine lactone, 3-oxo-C12-HSL), but not N-butanoyl-L-homoserine lactone (C4-HSL), induces apoptosis in macrophages and neutrophils. In the present study, the effects of active immunization with 3-oxo-C12-HSL-carrier protein conjugate on acute P. aeruginosa lung infection in mice were investigated. Immunization with 3-oxo-C12-HSL-BSA conjugate (subcutaneous, four times, at 2-week intervals) elaborated significant amounts of specific antibody in serum. Control and immunized mice were intranasally challenged with approximately 3 x 10(6) c.f.u. P. aeruginosa PAO1, and survival was then compared. All control mice died by day 2 post bacterial challenge, while 36 % of immunized mice survived to day 4 (P<0.05). Interestingly, bacterial numbers in the lungs did not differ between control and immunized groups, whereas the levels of pulmonary tumour necrosis factor (TNF)-alpha in the immunized mice were significantly lower than those of control mice (P<0.05). Furthermore, the extractable 3-oxo-C12-HSL levels in serum and lung homogenate were also significantly diminished in the immunized mice. Immune serum completely rescued reduction of cell viability by 3-oxo-C12-HSL-mediated apoptosis in macrophages in vitro. These results demonstrated that specific antibody to 3-oxo-C12-HSL plays a protective role in acute P. aeruginosa infection, probably through blocking of host inflammatory responses, without altering lung bacterial burden. The present data identify a promising potential vaccine strategy targeting bacterial quorum-sensing molecules, including autoinducers.

4-Butyrolactone↗

PubMed2006

Effect of age on prognosis in patients with gastric cancer.

BACKGROUND: The incidence of gastric cancer among the elderly has recently been increasing; however, the prognostic value of age in patients with gastric cancer remains elusive. METHODS: A total of 1473 patients with gastric cancer, who had undergone curative gastrectomy were reviewed to investigate the prognostic significance of age. RESULTS: Blood vessel invasion and differentiated type were more frequently observed in elderly than nonelderly patients (P < 0.0001) and elderly patients underwent limited lymph node dissection compared with nonelderly patients (P < 0.001). Moreover, chemotherapy was carried out in nonelderly patients more frequently than in elderly patients (P < 0.005). Ten-year survival rates were 70.2 and 81.4% in elderly and nonelderly patients, respectively, and the differences were statistically significant (P < 0.001). Postoperative mortality rates were 3.2 and 2.0% in elderly and nonelderly patients, respectively. Hematogenous recurrence was more frequently observed in elderly patients than nonelderly patients (P < 0.05). Multivariate analysis showed that age was an independent prognostic factor. CONCLUSIONS: Age clinically serves as a simple predictor of survival in patients with gastric cancer and should be taken into account along with conventional clinicopathological variables such as depth of invasion and lymph node metastasis.

Adenocarcinoma↗

PubMed2006

A tumor necrosis factor-alpha antagonist inhibits inflammatory bone resorption induced by Porphyromonas gingivalis infection in mice.

BACKGROUND: A tumor-necrosis factor-alpha (TNF-alpha) antagonist, the WP9QY peptide, was designed based on the crystal structure of the TNF-beta/TNF-receptor complex in order to overcome the disadvantages of macromolecules such as antibodies or soluble receptors by reducing the molecular size of TNF-alpha antagonists. It efficiently antagonizes the effect of TNF-alpha binding to the TNF receptor (I). OBJECTIVES: The aim of the present study was to assess the effects of the WP9QY peptide on inflammatory bone resorption and osteoclast formation in the periodontal pathogen-infection model. MATERIAL AND METHODS: Live Porphyromonas gingivalis ATCC 33277 was injected once daily for 6 days into the subcutaneous tissue overlying the calvariae in mice. At the same time, the WP9QY peptide (1 mg/kg, 2 mg/kg or 4 mg/kg per day) was administrated via osmotic minipumps for 7 days. Histological observations and the radiological assessments of the calvariae as well as bone mineral density measurements were performed. RESULTS: The WP9QY peptide significantly prevented the P. gingivalis-induced reduction in the bone mineral density at the calvariae. The histomorphometric assessments revealed the inhibitiory effects of the WP9QY peptide on the P. gingivalis-induced increase in the number of the inflammatory cells and in the area of sagittal suture at the calvariae. Furthermore, there was also an inhibitory effect on the P. gingivalis-induced increase in the number of osteoclasts per unit bone surface at the calvariae. CONCLUSION: These results suggest that the strategy for the design to reduce the molecular size of the TNF-alpha antagonists would be beneficial for the treatment of local inflammatory bone loss induced by periodontal-pathogen infection.

Analysis of Variance↗

PubMed2006

Cross-priming of cyclin B1, MUC-1 and survivin-specific CD8+ T cells by dendritic cells loaded with killed allogeneic breast cancer cells.

INTRODUCTION: The ability of dendritic cells (DCs) to take up whole tumor cells and process their antigens for presentation to T cells ('cross-priming') is an important mechanism for induction of tumor specific immunity. METHODS: In vitro generated DCs were loaded with killed allogeneic breast cancer cells and offered to autologous naïve CD8+ T cells in 2-week and/or 3-week cultures. CD8+ T cell differentiation was measured by their capacity to secrete effector cytokines (interferon-gamma) and kill breast cancer cells. Specificity was measured using peptides derived from defined breast cancer antigens. RESULTS: We found that DCs loaded with killed breast cancer cells can prime naïve CD8+ T cells to differentiate into effector cytotoxic T lymphocytes (CTLs). Importantly, these CTLs primed by DCs loaded with killed HLA-A*0201- breast cancer cells can kill HLA-A*0201+ breast cancer cells. Among the tumor specific CTLs, we found that CTLs specific for HLA-A2 restricted peptides derived from three well known shared breast tumor antigens, namely cyclin B1, MUC-1 and survivin. CONCLUSION: This ability of DCs loaded with killed allogeneic breast cancer cells to elicit multiantigen specific immunity supports their use as vaccines in patients with breast cancer.

Antigen Presentation↗

PubMed2005

Expression of inducible nitric oxide synthase is significantly correlated with expression of vascular endothelial growth factor and dendritic cell infiltration in patients with advanced gastric carcinoma.

OBJECTIVE: Nitric oxide (NO) is a product of L-arginine to L-citrulline conversion by nitric oxide synthase (NOS). The inducible form of NOS (iNOS) is one of three classes of NOS and the strongest producer of NO. It has been reported that NO correlates with angiogenesis and immune responses in some types of cancer, however, the correlations between iNOS expression, angiogenesis, and immune responses are still unclear in gastric carcinoma. METHODS: iNOS expression was determined in 135 gastric cancer patients by immunohistochemical procedures and compared with the expression of vascular endothelial growth factor (VEGF), microvessel (MV) density, and dendritic cell (DC) infiltration to evaluate the effect of iNOS on angiogenesis and immune responses in gastric carcinoma. RESULTS: iNOS expression was detected in 106 (78.5%) of 135 cases. There was a close correlation between iNOS expression and VEGF expression, a correlation with MV density and an inverse correlation with DC infiltration. There was no correlation between iNOS and p53 expression. The prognoses of patients whose tumors expressed iNOS were significantly worse than those of patients whose tumors did not express iNOS. Multivariate analysis indicated iNOS expression was an independent prognostic factor. CONCLUSION: iNOS might be associated with tumor progression by stimulating angiogenesis and suppressing immune responses in gastric carcinoma.

Adenocarcinoma↗

PubMed2005

Allogeneic gastric cancer cell-dendritic cell hybrids induce tumor antigen (carcinoembryonic antigen) specific CD8(+) T cells.

The development of protocols for the ex vivo generation of dendritic cells (DCs) has led to intensive research of their potential use in immunotherapy. Accumulating results show the efficacy of this treatment on melanomas which are highly immunogenic. However, its efficacy remains unclear in other tumors. In this study, allogeneic gastric cancer cell-DC hybrids were used to determine the efficacy of this type of immunotherapy in gastric cancer. Fusion cells of DC and allogeneic gastric cancer cells were generated by polyethylene glycol (PEG) and electrofusion. These hybrids were used to induce tumor associated antigen (TAA) specific cytotoxic T lymphocytes (CTLs). The DCs were successfully fused with the allogeneic gastric cancer cells resulting in hybrid cells. These hybrid cells were functional as antigen-presenting cell because they induced allogeneic CD4(+) T cells proliferation. CD8(+) T cells stimulated by the MKN-45-DC hybrid cells were able to kill MKN-45 when used for immunization. The CTLs killed another gastric cancer cell line, MKN-1, as well as a melanoma cell line, 888mel, suggesting the recognition of a shared tumor antigen. MKN-45 specific CTLs can recognize carcinoembryonic antigen (CEA), indicating that the killing is due to tumor antigens as well as alloantigens. This approach suggests the possible use of allogeneic gastric cancer cell-DC hybrids in DC based immunotherapy for gastric cancer treatment.

CD4-Positive T-Lymphocytes↗

PubMed2005

Laparoscopic-assisted intraperitoneal chemotherapy for patients with scirrhous gastric cancer.

BACKGROUND: The prognosis for patients with scirrhous gastric cancer (SGC) is extremely poor. To improve the patients' prognosis, laparoscopic-assisted intraperitoneal chemotherapy (IPC) was introduced for SGC. In this study, we analyzed whether IPC reduced the number of cancer cells in the peritoneal cavity of patients or changed the gene expression levels of cytokines in the peritoneal cavity. We also investigated whether IPC improved the prognosis of patients with SGC. METHODS: Total RNA was extracted from 50 ml of peritoneal wash from 11 SGC patients before and after cisplatin-based IPC. The gene expression levels of survivin, c-myc, transforming growth factor-beta (TGF-beta), interleukin-2 (IL-2), IL-6, and IL-12 were analyzed using real-time reverse transcription-polymerase chain reaction (RT-PCR) assays. Also, carcinoembrionic antigen (CEA) messenger RNA (mRNA) was used to identify the number of gastric cancer cells in peritoneal washes by the real-time RT-PCR method. The gene expression levels of cytokines and the number of cancer cells in the peritoneal cavity were compared before and after cisplatin-based IPC treatment. RESULTS: Before IPC, the gene expression of IL-2 from peritoneal washes of patients was significantly suppressed compared to the controls (p = 0.029); however, other gene expression levels did not differ. In 7 cases, more than 90% of the cancer cells were removed from the peritoneal cavity after cisplatin-based IPC. These 7 cases were named the IPC effective group, and the remaining 4 cases were named the IPC ineffective group. In the IPC effective group, elevated IL-2 and IL-6 genes were detected in 5 (71%) and in 6 (86%) after IPC. The correlation between IPC effectiveness and elevated gene expression after IPC (IL-2: p = 0.137, and IL-6: p = 0.044) was observed. However, the 50% survival period of the IPC effective group (9 months) was not different from that of that of the IPC ineffective group (6 months, p = 0.267). CONCLUSION: IPC effectiveness may correlate with elevation of gene expression of inflammatory cytokines, such as IL-2 and IL-6 in the peritoneal cavity after IPC. However, the prognostic benefits of IPC for SGC patients remain unclear.

Adenocarcinoma, Scirrhous↗

PubMed2005

Immunotherapy via dendritic cells.

The immune system evolved to protect us from microbes. The antigen (Ag)-nonspecific innate immunity and Ag-specific adaptive immunity synergize to eradicate the invading pathogen through cells, such as dendritic cells (DCZ7) and lymphocytes, and through their effector proteins including antimicrobial peptides, complement, and antibodies. Its intrinsic complexity renders the immune system prone to dysfunction including cancer, autoimmunity, chronic inflammation and allergy. DCs are unique in their capacity to induce and regulate immune responses and are therefore attractive candidates for immunotherapy. However, DCs consist of distinct subsets with common as well as unique functions that lead to distinct types of immune responses. Therefore, understanding DC heterogeneity and their role in immunopathology is critical to design better strategies for immunotherapy. Indeed, what we learn from studying autoimmunity will help us induce strong vaccine specific immunity, either protective, as in the case of microbes, or therapeutic, as in the case of tumors.

Animals↗