Abdel-Aziz Zidan | Damanhour University (original) (raw)

Papers by Abdel-Aziz Zidan

Introduction: Acute lymphoblastic leukemia (ALL) is the most common cancer diagnosed in children.... more Introduction: Acute lymphoblastic leukemia (ALL) is the most common cancer diagnosed in children. The precise mechanism behind the relapse in this disease is not clearly known. One possible mechanism could be the accumulation of immunosuppressive cells, including myeloid-derived suppressor cells (MDSCs) and T regulatory cells (T regs) which we and others have reported to mediate suppression of anti-tumor immune responses. Aim: In this study, we aimed to analyze the numbers of these cells in a population of BALL pediatric patients. Methods: Peripheral blood samples withdrawn from BALL pediatric patients (n ¼ 45 before, during and after the induction phase of chemotherapy. Using multi parametric flow cytometric analysis. MDSCs were identified as Lin – HLA-DR – CD33 þ CD11b þ ; and T reg cells were defined as CD4 þ CD25 þ CD127 –=low. Results: Early diagnosed BALL patients showed significant increases in the numbers of MDSCs and T regs as compared to healthy volunteers. During induction of chemotherapy, however, the patients showed higher and lower numbers of MDSCs and T reg cells, respectively as compared to early diagnosed patients (i.e., before chemotherapy). After induction of chemotherapy, the numbers of MDSCs and T reg cells showed higher increases and decreases, respectively as compared to the numbers in patients during chemotherapy. Conclusion: Our results indicate that BALL patients harbor high numbers of both MDSCs and T regs cells. This pilot study opens a new avenue to investigate the mechanism mediating the emergence of these cells on larger number of BALL patients at different treatment stages.

Infected patients with chronic hepatitis C virus (HCV) showed high numbers of myeloid-derived sup... more Infected patients with chronic hepatitis C virus (HCV) showed high numbers of myeloid-derived suppressor cells (MDSCs) which are known to suppress the immune response. Given that microRNAs regulate the expression of many genes, it is important to test whether MDSCs correlate with altered miRNA expression. Aim: The present study aimed to assess the expression of miR-29, 122 and 155 in chronic HCV patients under interferon (IFN) therapy and their correlation with the frequency of MDCS. A total of 28 subjects, including eighteen chronic HCV patients, and 10 healthy volunteers were enrolled in this study. MiR-29, 122 and 155 were evaluated using real-time-polymerase chain reaction (RT-PCR). Flow cytometric analysis was performed to evaluate the MDSCs which defined as Lin-HLA-DR-CD33 + CD11b +. Results: miR-29 and 122 expressions in HCV patients showed significant decrease when compared to their control. However, there was an increase (but non-significance) in miR-155 in HCV patients than control subjects. Both relative and absolute numbers of MDSCs were increased in the peripheral blood in HCV patients as compared to control subjects. Moreover, non-significance change in IFNα/β receptors was observed in HCV patients as compared to control subjects. Conclusion: High numbers of MDSCs in chronic HCV patients correlate with low expression of miR-29 and122.

Chronic hepatitis C virus (HCV) infection and hepatocellular carcinoma (HCC) resulted in dysfunct... more Chronic hepatitis C virus (HCV) infection and hepatocellular carcinoma (HCC) resulted in dysfunction of the immune response, in particular, dendritic cells (DCs). Stimulation and reactivation of DCs could restore the immune responses in this disease. Our previous study revealed that a synthetic double-stranded RNA (polyI:C) recognized by toll-like receptor 3 (TLR3) induced a potent innate immune response and had an impact on DCs both ex vivo and in vivo. The current study was aimed to generate and maturate DCs from peripheral blood mononuclear cells (PBMCs) of healthy controls and patients with HCV and HCC. Fresh peripheral blood (PB) was collected from healthy controls, patients with chronic HCV or patients with hepatocellular carcinoma (HCC). PBMCs were isolated and cultured for 6 days in RPMI-1640 supplemented with GM-CSF and rhIL-4 (10 ng/mL each). Poly(I:C) was added to the culture on day 6 and the cells were harvested on day 7. Phenotypic analysis of DCs and their maturation markers were assessed using flow cytometry. DCs were generated from adherent PBMCs of healthy donors or patients with HCV or HCC. Interestingly, the addition of poly(I:C) induced expansion and maturation of DCs as evidenced by the expression of HLA-DR and CD11bCD11c surface molecules on the DCs generated from all groups. In conclusion, DCs can be ex vivo generated from control or patients with HCV or HCC in response to external stimulation. These results may be a promising tool for a therapeutic vaccine against HCV infection.

Abd-Elsalam (2018) High numbers of myeloid derived suppressor cells in peripheral blood and ascit... more Abd-Elsalam (2018) High numbers of myeloid derived suppressor cells in peripheral blood and ascitic fluid of cirrhotic and HCC patients, Immunological Investigations, 47:2, 169-180,

Senna & Maha El Demellawy (2017) IFN-α-based treatment of patients with chronic HCV show increase... more Senna & Maha El Demellawy (2017) IFN-α-based treatment of patients with chronic HCV show increased levels of cells with myeloid-derived suppressor cell phenotype and of IDO and NOS ABSTRACT Introduction: Hepatitis C virus (HCV) infection causes chronic hepatitis, which is often associated with suppressed anti-HCV immune responses. We have recently reported accumulation of myeloid-derived suppressor cells (MDSCs) and suppressed immunity in cancer patients. Aim: The main aim of this study was to determine whether chronic HCV patients harbor high of MDSCs in general and in nonresponders to IFN-based therapy in particular as well as to analyze the immune suppressive molecules. Methods: Peripheral blood samples withdrawn from 154 patients with chronic HCV infection and were categorized into responders and nonresponders based on viral titer upon IFN-a treatment. Results: The relative and absolute numbers of MDSCs defined as Lin À /HLA-DR À /CD33 þ /CD11b þ increased in all HCV patients, where they were higher in nonresponders than in responders. Additionally, the levels of MDSCs after 4–6 months of treatment in responders were lower than during the course of treatment. The responders also showed higher levels of IL-2 coincided with increased numbers of dendritic cells (DCs), CD4 þ and CD8 þ T cells. The levels of total NOS and IDO were also higher in nonresponders as compared to responders and healthy controls, while the expression levels of CD3f was lower in responders as compared to nonresponders and healthy volunteers. Conclusion: Chronic HCV patients harbor high numbers of MDSCs, which are higher in nonresponders than in responders. The higher numbers of MDSCs associated with increases in the suppressing factors.

Immunologic Research, 2013

CD62L governs the circulation of CD8(+) T cells between lymph nodes and peripheral tissues, where... more CD62L governs the circulation of CD8(+) T cells between lymph nodes and peripheral tissues, whereby the expression of CD62L by CD8(+) T cells promotes their recirculation through lymph nodes. As such, CD62L participates in the fate of adoptively transferred CD8(+) T cells and may control their effectiveness for cancer immunotherapy, including settings in which host preconditioning results in the acute lymphopenia-induced proliferation of the transferred cells. Indeed, previous studies correlated CD62L expression by donor CD8(+) cells with the success rate of adoptive cell therapy (ACT). Here, we analyzed the functions and fate of ex vivo-activated, tumor-specific CD62L(-/-) CD8(+) T cells in a mouse melanoma model for ACT. Unexpectedly, we observed that CD62L(-/-) CD8(+) T cells were functionally indistinguishable from CD62L(+/+) CD8(+) T cells, i.e., both greatly expanded in cyclophosphamide preconditioned animals, controlled subcutaneously and hematogenously spreading tumors, and generated anti-tumor-specific CD8(+) T cell memory. Moreover, even in hosts with rudimentary secondary lymphoid organs (LT(-/-) animals), CD8(+) T cells with and without CD62L expanded equivalently to those adoptively transferred into wild-type animals. These results put into question the utility of CD62L as a predictive biomarker for the efficacy of ex vivo-expanded T cells after ACT in lymphopenic conditions and also offer new insights into the homing, engraftment, and memory generation of adoptively transferred ex vivo-activated CD8(+) T cells.

American journal of cancer research, Jan 30, 2011

Adoptive T-cell therapy holds great promise for the treatment of metastatic melanoma. However, pr... more Adoptive T-cell therapy holds great promise for the treatment of metastatic melanoma. However, prohibitive costs associated with current technology required for culture and expansion of tumor-reactive T-cells, the need for intense preconditioning regimens to induce lymphopenia, and the unpredictable anti-tumor effect of adoptively transferred T-cells remain significant impediments for its clinical implementation. Here we report a simplified combinatorial approach that involves short activation of CD8(+) T cells in the presence of IL-12 followed by adoptive transfer into tumor bearing animals after a single injection of cyclophosphamide. This approach resulted in complete eradication of B16 melanoma, and the establishment of long term immunological memory capable of fully protecting mice after a second B16 melanoma challenge. The activated donor cells were unique because they simultaneously exhibited traits for cytotoxic effector function, central memory-like, homing, and senescence....

The Journal of Immunology, May 1, 2012

Background: Acute lymphoblastic leukemia (ALL) is considered as one of the most common cancer in ... more Background: Acute lymphoblastic leukemia (ALL) is considered as one of the most common cancer in pediatric malignancies. Among ALL, B-cell Acute Lymphoblastic Leukemia (B-ALL) represents 80% to 85% of the childhood ALL. Problem: Although anti B‑ALL chemotherapy kill B‑ALL, it associates with alteration in the numbers of CD4+ and CD8+ T‑cells, and thus impacts the overall immunity. Aim: To evaluate the impact of anti B‑ALL on the numbers of CD4+ and CD8+ T‑cells in correlation to the numbers of CD10+ B cells in B‑ALL pediatric patients. Materials and Methods: Peripheral blood samples were drawn from previously diagnosed B‑ALL before (n = 10 cases) and after (n = 10 cases) chemotherapy as well as from healthy controls (n = 10 cases). The numbers of CD4+, CD8+ T‑cells and CD10+ B cells were measured in these samples by flow cytometry. Results: As expected, the numbers of CD10+ B‑cells were increased in B‑ALL patients before chemotherapy which were associated with increases in the numbers of CD4+ and CD8+ T‑cells. Chemotherapy of B‑ALL patients, during the induction phase, induced dramatic decreases in the numbers of CD10+ B cells, which were associated with decreases in the numbers of CD4+ and CD8+ T‑cells. Tin spite of this alteration, the ratio of CD4/CD8 in B‑ALL patients were remained similar before and after chemotherapy as compared to those in healthy controls. Conclusion: Anti B‑ALL chemotherapy induces alterations in the frequencies of T‑cell subsets. Given the importance of these cells in anti‑tumor immunity, our data may lead to further studies to investigate the different subsets of these cells, in particular regulatory T‑cells.
Key words: B‑acute lymphoblastic leukemia, B‑ALL, B‑cells, cancer, CD10, CD4, CD8, chemotherapy, T‑cells, Tregs

We have reported recently that Interleu-kin-12 (IL-12) released from poly-N-acetyl glucosa-mine g... more We have reported recently that Interleu-kin-12 (IL-12) released from poly-N-acetyl glucosa-mine gel matrix (F2 gel/IL-12) is more effective than free IL-12 to enhance vaccination of mice with Schistosoma soluble worm antigen preparation. The aim of this study is to evaluate the effect of F2 gel/IL-12 on the inflammatory responses in mice undergoing schistosomiasis infection in absence of vaccination. To achieve this, mice undergoing Schistosoma man-soni infection or cured from this infection, after treatment with praziquantil (PZQ), were treated with subcutaneous injection of IL-12 for 3 consecutive days or once with F2 gel loaded with IL-12 (F2 gel/IL-12). The treatment was started on day 35 days after infection. For infection, mice were infected with 100 cercariae of S. mansoni using tail immersion method. We found that treatment with F2 gel/IL-12 induced significant decreases in the egg burden with a moderate reduction in the size of granuloma and decrease in the cellular granulomatous reaction in the lung as compared to infected mice treated with IL-12. These effects of F2 gel/IL-12 were more pronounced in infected mice previously treated with the anti-schis-tosomal drug PZQ. The total numbers of white blood cells in all treated mice showed similar profile. Treatment with IL-12 or F2 gel/IL-12, however, showed significant reduction in the number of mono-nuclear cells when compared with non-treated infected mice. In conclusion, this study showed the ability of IL-12 released from F2 gel to lower the inflammatory response to Schistosoma infection even in absence of vaccination.

Senna & Maha El Demellawy (2017): IFN-α-based treatment of patients with chronic HCV show increas... more Senna & Maha El Demellawy (2017): IFN-α-based treatment of patients with chronic HCV show increased levels of cells with myeloid-derived suppressor cell phenotype and of IDO and NOS, Immunopharmacology and Immunotoxicology, ABSTRACT Introduction: Hepatitis C virus (HCV) infection causes chronic hepatitis, which is often associated with suppressed anti-HCV immune responses. We have recently reported accumulation of myeloid-derived suppressor cells (MDSCs) and suppressed immunity in cancer patients. Aim: The main aim of this study was to determine whether chronic HCV patients harbor high of MDSCs in general and in nonresponders to IFN-based therapy in particular as well as to analyze the immune suppressive molecules. Methods: Peripheral blood samples withdrawn from 154 patients with chronic HCV infection and were categorized into responders and nonresponders based on viral titer upon IFN-a treatment. Results: The relative and absolute numbers of MDSCs defined as Lin À /HLA-DR À /CD33 þ /CD11b þ increased in all HCV patients, where they were higher in nonresponders than in responders. Additionally, the levels of MDSCs after 4–6 months of treatment in responders were lower than during the course of treatment. The responders also showed higher levels of IL-2 coincided with increased numbers of dendritic cells (DCs), CD4 þ and CD8 þ T cells. The levels of total NOS and IDO were also higher in nonresponders as compared to responders and healthy controls, while the expression levels of CD3f was lower in responders as compared to nonresponders and healthy volunteers. Conclusion: Chronic HCV patients harbor high numbers of MDSCs, which are higher in nonresponders than in responders. The higher numbers of MDSCs associated with increases in the suppressing factors.

Acute lymphoblastic leukemia (ALL) is biologically and clinically considered as a heterogeneous n... more Acute lymphoblastic leukemia (ALL) is biologically and clinically considered as a heterogeneous neoplasm of lymphoid progenitor cells. About 85% of children with ALL are diagnosed as B-ALL, expressing CD19; the typical marker of normal B cells. Problem: Given that the chemotherapy associated with leucopenia, in particular myeloid cells (CD33+ cells), Aim: the main aim of this study was to analyze the numbers of these cells in children with B-ALL before and after induction of chemotherapy. Materials and Methods: The frequencies of CD33+ myeloid cells and CD19+ B-cells were analyzed in the peripheral blood patients before (n = 10) and after (n = 10) induction of chemotherapy as well as in healthy volunteers (n = 10) using multiparametric flow cytometry. Results: As expected, B-ALL patients showed high numbers of CD19+ cells before induction of chemotherapy; where the numbers of these cells were reduced upon the induction of chemotherapy. CD33+ myeloid cells showed decrease in numbers in B-ALL patients before chemotherapy as compared to healthy control volunteers. Interestingly, treatment of B-ALL patients with chemotherapy-induced almost recovery of the numbers of these cells. Conclusion: CD33+ myeloid cells are increased in numbers after induction of chemotherapy, indicating to a dynamic mobilization or differentiation of their precursors into circulation. This study opens a new avenue to characterize the phenotype and function of these cells in different hematological malignancies; in particular, they may harbor regulatory cells.

Background: Granulocyte colony stimulating factor (G-CSF) is used in clinical practice to mobiliz... more Background: Granulocyte colony stimulating factor (G-CSF) is used in clinical practice to mobilize neutrophils alone or in combination with chemotherapy. However, its influence in physiological indices has not been addressed well in certain animal models such as Wistar rats. Aims: To evaluate the single and combinatorial effects of G-CSF and cyclophosphamide (CTX) on physiological indices in Wistar rat. Materials and Methods: Naïve female Wistar rats were treated with subcutaneous injection of pharmaceutical benefits scheme, (5 μL/day/rat) G-CSF for 5 consecutive days and single intraperitoneal injection of CTX (4 mg/rat). Body weights were obtained daily. Rats were sacrificed 1-day after the last injection to obtain different organ weight and to analyze the physiological indices in plasma and the liver. Results: G-CSF alone induced increases in body weight, splenomegaly, white blood cells, platelets, and alanine aminotransferase (ALT) activity. It, however, decreased neutrophils and monocytes, aspartate aminotransferase (AST) activity, red blood cells and hemoglobin level. CTX alone induced decreases in body weight, white blood cells, neutrophils, red blood cells and hemoglobin level. It, however, increased spleen weight, lymphocytes, monocytes, ALT activity and AST. G-CSF + CTX induced increases in body weight, splenomegaly, lymphocytes and ALT. It, however, decreased white blood cells, platelets number, neutrophils, monocytes, red blood cells and hemoglobin level. Conclusion: Among different physiological indices, treatment with single or combinatorial G-CSF increases the total number of white blood cells in Wistar rats which need to be considered while using this model animal disease.

Genomic signal processing (GSP) is the engineering area concerned with genomic data analysis usin... more Genomic signal processing (GSP) is the engineering area concerned with genomic data analysis using digital signal processing techniques by conversion of the genomic sequence into numerical one as a first step. One of the central issues in GSP is maximizing the accuracy of protein coding region prediction in a given DNA sequence. In this study advanced DNA numerical representations (genetic code context, 2-bit binary and EIIP) were compared in terms of their sensitivity, specificity and correlation coefficient for maximizing the accuracy of the prediction of protein coding region. Digital filters based technique has been applied to extract the period 3 components and removing the undesired noise from the DNA sequence. Results from implementation of the technique on 8 human genes showed that the 2-bit binary representation scheme associated with the used filtering technique has the maximum accuracy compared to the other tested schemes. These findings suggests that the 2-bit binary representation scheme greatly enhances the prediction accuracy of the protein coding region using digital filters opening a new avenue to use this scheme in different applications.

Immunol Res., Nov 12, 2013

CD62L governs the circulation of CD8+ T cells between lymph nodes and peripheral tissues, whereby... more CD62L governs the circulation of CD8+ T cells between lymph nodes and peripheral tissues, whereby the expression of CD62L by CD8+ T cells promotes their recirculation through lymph nodes. As such, CD62L participates in the fate of adoptively transferred CD8+ T cells and may control their effectiveness for cancer immunotherapy, including settings in which host preconditioning results in the acute lymphopenia-induced proliferation of the transferred cells. Indeed, previous studies correlated CD62L expression by donor CD8+ cells with the success rate of adoptive cell therapy (ACT). Here, we analyzed the functions and fate of ex vivo-activated, tumor-specific CD62L-/- CD8+ T cells in a mouse melanoma model for ACT. Unexpectedly, we observed that CD62L-/- CD8+ T cells were functionally indistinguishable from CD62L+/+ CD8+ T cells, i.e., both greatly expanded in cyclophosphamide preconditioned animals, controlled subcutaneously and hematogenously spreading tumors, and generated anti-tumor-specific CD8+ T cell memory. Moreover, even in hosts with rudimentary secondary lymphoid organs (LT-/- animals), CD8+ T cells with and without CD62L expanded equivalently to those adoptively transferred into wild-type animals. These results put into question the utility of CD62L as a predictive biomarker for the efficacy of ex vivo-expanded T cells after ACT in lymphopenic conditions and also offer new insights into the homing, engraftment, and memory generation of adoptively transferred ex vivo-activated CD8+ T cells.

Diabetes is now one of the most common un-communicable diseases worldwide. Few studies have dealt... more Diabetes is now one of the most common un-communicable diseases worldwide. Few studies have dealt specifically with the potential therapeutic effect of TNF-α suppressor to decrease oxidative stress markers in patients with diabetes. The aim of this study was to investigate the potential therapeutic and toxic effect of the direct injection of the anti-TNF-α on oxidative stress mediators, proinflammatory cytokines and vascular risk factors associated with diabetes on diabetic rats. Methods: diabetes was induced by streptozotocin, three weeks after the - induction of diabetes, a polyclonal anti-mouse/rat TNF-α rabbit serum was injected in the treated group and sacrificed after 4 weeks. The expression of TNF-α mRNA was measured by RT-PCR. The levels of TNF-α, VEGF, IL-2, IL- 6, HSP-70, troponin-t, 8-OHdG, ICAM-1 and VCAM-1 were evaluated using ELISA. Myeloperoxiase (MPO) and total peroxides (TPs) levels were estimated by biochemical reactions. Results: the treatment of diabetic rats with the anti-TNF-α caused a significant decrease in the TNF-α mRNA expression, which were paralleled with the decreased levels of TNF-α, IL-6, MOP, HSP-70, ICAM-1, VCAM-1, troponin-t and 8-OHdG in the blood serum. On the contrary, all were highly expressed in the diabetic group that may be the leading reasons for the DNA damage and cell loss. Data revealed that TNF-α, HSP-70, IL-6, MPO and adhesion molecules when expressed in diabetic rats, collectively induce dramatic changes. Conclusion: these new findings suggested that targeting TNF-α could effectively reduce expressions of MCP-1, HSP-70, troponin-t, 8-OHdG and VCAM- 1, along with prominent reduction in MPO and IL-6 levels.

Clinical trials in a number of solid tumor indications have shown that the addition of NOV-002 (a... more Clinical trials in a number of solid tumor indications have shown that the addition of NOV-002 (a formulation of disodium glutathione disulfide) to a range of cytotoxic chemotherapeutic regimens potentiates their anti-tumor efficacy. However, the specific mechanisms involved remain unclear. Previous in vitro studies demonstrated that NOV-002 generates oxidative signals in human tumor cell lines resulting in apoptosis and decreased proliferation. In addition, NOV-002 has been reported to display in vivo immunomodulatory properties in oncology settings. Hence, NOV-002: (i) significantly increases circulating T-lymphocyte subsets [CD4+, CD8+, NK-T lymphocytes] in non-small lung cancer patients receiving chemotherapy plus NOV-002 vs. chemotherapy alone; (ii) reverses T-cell suppressive effect of myeloid suppressor cells in mice; (iii) potentiates anti-tumor effect of adoptive immunotherapy in a mouse melanoma model; (iv) increases intra-tumoral memory T-cells and anti-tumor immune responsiveness in a mouse model of ovarian cancer. Here, we sought to test the hypothesis that NOV-002 potentiates the anti-tumor effect of chemotherapy through immune-mediated mechanisms. To this end in the CT26 murine colon cancer model, tumor-bearing mice were treated with NOV-002 (25 mg/kg, i.p.) or saline (daily on days 1-14, then Monday-Friday, beginning 5 days post-tumor injection until tumor progression), followed by 200mg/kg cyclophosphamide (CTX) on days 6 and 9. In three independent experiments we found that while NOV-002 alone had only a modest effect on tumor growth rate, the addition of NOV-002 to CTX resulted in significantly slower tumor growth compared to CTX alone. Mean overall survival was significantly longer in CTX/NOV mice [90 vs 47 days; P=0.005]. Interestingly, all mice receiving CTX alone developed tumors, while approximately 40% of CTX/NOV-002 mice showed no tumor development. To further investigate whether failure of tumor development in these mice was due to an immune mechanism, they underwent tumor rechallenge. In two independent experiments only 1/7 mice (14%) developed tumors after rechallenge. To test the contribution of memory T-cells, which are known to home to the bone marrow, CTX/NOV-002 mice with tumor failure were sacrificed and marrows adoptively transferred to mice bearing 7 day old CT26 tumors. A significant delay in tumor progression was observed in mice receiving adoptively transferred marrow suggesting that the immunologic memory generated after CTX/NOV-002 treatment was sufficient to effectively prevent or regress tumor formation. Taken together, these data provide further support to the hypothesis that, when combined with chemotherapy, NOV-002’s anti-tumor efficacy may be due at least in part to enhancement of anti-tumor cellular immune responsiveness.

Recently, we showed that post cyclophosphamide (CTX) microenvironment benefits the function of tr... more Recently, we showed that post cyclophosphamide (CTX) microenvironment benefits the function of transferred T cells. Analysis of the kinetics of cellular recovery after CTX treatment showed that a single 4 mg/mouse CTX treatment decreased the absolute number of leukocytes in the peripheral blood (PBL) at days 3-15, and in the spleen and bone marrow (BM) at days 3-6. The absolute numbers of CD11c+CD11b- and CD11c+CD11b+ dendritic cells (DCs), CD11b+ and Ly6G+ myeloid cells, T and B cells, CD4+CD25+ T regulatory (Treg) cells, and NK1.1+ cells also decreased. The cell numbers returned to control levels during the recovery phase. The absolute numbers of B cells remained low for 3 weeks. The numbers of DCs increased in PBL and spleen at day 9 but returned to control levels at day 15. These data indicate that CTX alters the cellular microenvironment in kinetics that might be precisely targeted to benefit the host.

Immunologic Research, 2013

American journal of cancer research, Jan 30, 2011

The Journal of Immunology, May 1, 2012

Immunol Res., Nov 12, 2013