InVivoMAb anti-mouse CD20
Product Details
The MB20-11 monoclonal antibody reacts with mouse CD20. CD20 is a B cell-specific 33-37 kDa transmembrane protein which is also known as B-lymphocyte antigen, B1, and Bp35. CD20 plays roles in intracellular calcium regulation and B cell activation and is critical for an optimal B cell immune response against T-independent antigens. CD20 is first expressed after the induction of CD19 together with IgM during the pre-B to immature B cell transition in the bone marrow. Itās expression then increases during maturation with almost all mature B cells expressing some level of CD20. However, CD20 is not expressed by plasma blasts or plasma cells. CD20 is expressed by most B cell neoplasms and is useful in diagnosing B cell lymphomas and leukemia. Many anti-CD20 monoclonal antibodies are currently being used to successfully treat leukemia, lymphomas, and various autoimmune diseases. A single injection of the MB20-11 antibody has been reported to deplete circulating B cells in mice within 1 hour of treatment, with a durable effect for 57 days before B cells begin to repopulate in the blood and spleen.Specifications
| Isotype | Mouse IgG2c, Īŗ |
|---|---|
| Recommended Isotype Control(s) | InVivoMAb mouse IgG2c isotype control, anti-dengue virus |
| Recommended Dilution Buffer | InVivoPure pH 7.0 Dilution Buffer |
| Conjugation | This product is unconjugated. Conjugation is available via our Antibody Conjugation Services. |
| Immunogen | Mouse CD20-GFP transfected 300.19 cells |
| Reported Applications |
in vivo B cell depletion Western blot |
| Formulation |
PBS, pH 7.0 Contains no stabilizers or preservatives |
| Endotoxin |
<2EU/mg (<0.002EU/Ī¼g) Determined by LAL gel clotting assay |
| Purity |
>95% Determined by SDS-PAGE |
| Sterility | 0.2 Āµm filtration |
| Production | Purified from cell culture supernatant in an animal-free facility |
| Purification | Protein A |
| RRID | AB_2894775 |
| Molecular Weight | 150 kDa |
| Storage | The antibody solution should be stored at the stock concentration at 4Ā°C. Do not freeze. |
Additional Formats
Recommended Products
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Recommended Isotype Control(s)
InVivoMAb mouse IgG2c isotype control, anti-dengue virus
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Recommended Dilution Buffer
InVivoPure pH 7.0 Dilution Buffer
in vivo B cell depletion
Haas, K. M., et al. (2010). "Protective and pathogenic roles for B cells during systemic autoimmunity in NZB/W F1 mice" J Immunol 184(9): 4789-4800. PubMed
Delineating the relative contributions of B lymphocytes during the course of autoimmune disease has been difficult. Therefore, the effects of depleting all mature B cells using a potent CD20 mAb, or of depleting circulating and marginal zone B cells using a ligand-blocking CD22 mAb, were compared in NZB/W F(1) mice, a model for human systemic lupus erythematosus. Single low-dose mAb treatments depleted B cells efficiently in both NZB/W F(1) and C57BL/6 mice. Prophylactic B cell depletion by repeated CD20 mAb treatments prolonged survival during pristane-accelerated lupus in NZB/W F(1) mice, whereas CD22 mAb had little effect. Despite effective B cell depletion, neither mAb treatment prevented autoantibody generation. In addition, CD20, CD22, and control mAb-treated NZB/W F(1) mice developed anti-mouse IgG autoantibodies in contrast to parental NZB and NZW strains, which may have reduced the effectiveness of B cell depletion. Despite this, low-dose CD20 mAb treatment initiated in 12-28-wk-old mice, and administered every 4 wk thereafter, significantly delayed spontaneous disease in NZB/W F(1) mice. By contrast, B cell depletion initiated in 4-wk-old mice hastened disease onset, which paralleled depletion of the IL-10-producing regulatory B cell subset called B10 cells. B10 cells were phenotypically similar in NZB/W F(1) and C57BL/6 mice, but were expanded significantly in young NZB/W F(1) mice. Thus, B cell depletion had significant effects on NZB/W F(1) mouse survival that were dependent on the timing of treatment initiation. Therefore, distinct B cell populations can have opposing protective and pathogenic roles during lupus progression.
in vivo B cell depletion
Hamaguchi, Y., et al. (2006). "Antibody isotype-specific engagement of Fcgamma receptors regulates B lymphocyte depletion during CD20 immunotherapy" J Exp Med 203(3): 743-753. PubMed
CD20 monoclonal antibody (mAb) immunotherapy is effective for lymphoma and autoimmune disease. In a mouse model of immunotherapy using mouse anti-mouse CD20 mAbs, the innate monocyte network depletes B cells through immunoglobulin (Ig)G Fc receptor (FcgammaR)-dependent pathways with a hierarchy of IgG2a/c>IgG1/IgG2b>IgG3. To understand the molecular basis for these CD20 mAb subclass differences, B cell depletion was assessed in mice deficient or blocked for stimulatory FcgammaRI, FcgammaRIII, FcgammaRIV, or FcR common gamma chain, or inhibitory FcgammaRIIB. IgG1 CD20 mAbs induced B cell depletion through preferential, if not exclusive, interactions with low-affinity FcgammaRIII. IgG2b CD20 mAbs interacted preferentially with intermediate affinity FcgammaRIV. The potency of IgG2a/c CD20 mAbs resulted from FcgammaRIV interactions, with potential contributions from high-affinity FcgammaRI. Regardless, FcgammaRIV could mediate IgG2a/b/c CD20 mAb-induced depletion in the absence of FcgammaRI and FcgammaRIII. In contrast, inhibitory FcgammaRIIB deficiency significantly increased CD20 mAb-induced B cell depletion by enhancing monocyte function. Although FcgammaR-dependent pathways regulated B cell depletion from lymphoid tissues, both FcgammaR-dependent and -independent pathways contributed to mature bone marrow and circulating B cell clearance by CD20 mAbs. Thus, isotype-specific mAb interactions with distinct FcgammaRs contribute significantly to the effectiveness of CD20 mAbs in vivo, which may have important clinical implications for CD20 and other mAb-based therapies.
in vivo B cell depletion
Uchida, J., et al. (2004). "Mouse CD20 expression and function" Int Immunol 16(1): 119-129. PubMed
CD20 plays a role in human B cell proliferation and is an effective target for immunotherapy. In this study, mouse CD20 expression and biochemistry were assessed for the first time using a new panel of CD20-specific mAb, with CD20 function assessed using CD20-deficient (CD20(-/-)) mice. CD20 expression was B cell restricted and was initiated during late pre-B cell development. The frequency and density of CD20 expression increased during B cell maturation in the bone marrow, with a subpopulation of transitional IgM(hi) B cells expressing higher CD20 levels than the majority of mature recirculating B cells. Transitional T1 B cells in the spleen also expressed high CD20 levels, providing a useful new marker for this B cell subset. In CD20(-/-) mice, immature and mature B cell IgM expression was approximately 20-30% lower relative to B cells from wild-type littermates. In addition, CD19-induced intracellular calcium responses were significantly reduced in CD20(-/-) B cells, with a less dramatic effect on IgM-induced responses. These results reveal a role for CD20 in transmembrane Ca(2+) movement in mouse primary B cells that complements previous results obtained using human CD20 cDNA-transfected cell lines. Otherwise, B cell development, tissue localization, signal transduction, proliferation, T cell-dependent antibody responses and affinity maturation were normal in CD20(-/-) mice. Thus, mouse and human CD20 share similar patterns of expression and function. These studies thereby provide an animal model for studying CD20 function in vivo and the molecular mechanisms that influence anti-CD20 immunotherapy.
in vivo B cell depletion
Uchida, J., et al. (2004). "The innate mononuclear phagocyte network depletes B lymphocytes through Fc receptor-dependent mechanisms during anti-CD20 antibody immunotherapy" J Exp Med 199(12): 1659-1669. PubMed
Anti-CD20 antibody immunotherapy effectively treats non-Hodgkinās lymphoma and autoimmune disease. However, the cellular and molecular pathways for B cell depletion remain undefined because human mechanistic studies are limited. Proposed mechanisms include antibody-, effector cell-, and complement-dependent cytotoxicity, the disruption of CD20 signaling pathways, and the induction of apoptosis. To identify the mechanisms for B cell depletion in vivo, a new mouse model for anti-CD20 immunotherapy was developed using a panel of twelve mouse anti-mouse CD20 monoclonal antibodies representing all four immunoglobulin G isotypes. Anti-CD20 antibodies rapidly depleted the vast majority of circulating and tissue B cells in an isotype-restricted manner that was completely dependent on effector cell Fc receptor expression. B cell depletion used both FcgammaRI- and FcgammaRIII-dependent pathways, whereas B cells were not eliminated in FcR common gamma chain-deficient mice. Monocytes were the dominant effector cells for B cell depletion, with no demonstrable role for T or natural killer cells. Although most anti-CD20 antibodies activated complement in vitro, B cell depletion was completely effective in mice with genetic deficiencies in C3, C4, or C1q complement components. That the innate monocyte network depletes B cells through FcgammaR-dependent pathways during anti-CD20 immunotherapy has important clinical implications for anti-CD20 and other antibody-based therapies.
- FC/FACS,
- Immunology and Microbiology
Interaction of the endogenous antibody response with activating FcĪ³Rs enhance control of Mayaro virus through monocytes.
In PLoS Pathogens on 1 February 2025 by Dunagan, M. M., DƔbilla, N., et al.
Mayaro virus (MAYV) is an emerging arbovirus. Previous studies have shown antibody Fc effector functions are critical for optimal monoclonal antibody-mediated protection against alphaviruses; however, the requirement of Fc gamma receptors (FcĪ³Rs) for protection during natural infection has not been evaluated. Here, we showed mice lacking activating FcĪ³Rs (FcRĪ³-/-) developed prolonged clinical disease with increased MAYV in joint-associated tissues. Viral reduction was associated with anti-MAYV cell surface binding antibodies rather than neutralizing antibodies. Lack of Fc-FcĪ³R engagement increased the number of monocytes present in the joint-associated tissue through chronic timepoints. Single-cell RNA sequencing showed elevated levels of pro-inflammatory monocytes in joint-associated tissue with increased MAYV RNA present in FcRĪ³-/- monocytes and macrophages. Transfer of FcRĪ³-/- monocytes into wild type animals was sufficient to increase virus in joint-associated tissue. Overall, this study suggests that engagement of antibody Fc with activating FcĪ³Rs promotes protective responses during MAYV infection and prevents a pro-viral role for monocytes. Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
- Mus musculus (House mouse),
- Cancer Research
Blockade of TGF-Ī² and PD-L1 by bintrafusp alfa promotes survival in preclinical ovarian cancer models by promoting T effector and NK cell responses.
In British Journal of Cancer on 1 June 2024 by Kment, J., Newsted, D., et al.
Failure of immunotherapy in high-grade serous ovarian cancer (HGSC) may be due to high levels of transforming growth factor-Ī² (TGF-Ī²) in ascites or tumour immune microenvironment (TIME). Here, we test whether coordinated blockade of TGF-Ī² and PD-L1 with bintrafusp alfa (BA) can provoke anti-tumour immune responses in preclinical HGSC models. BA is a first-in-class bifunctional inhibitor of TGF-Ī² and PD-L1, and was tested for effects on overall survival and altered TIME in syngeneic HGSC models. Using a mouse ID8-derived HGSC syngeneic model with IFNĪ³-inducible PD-L1 expression, BA treatments significantly reduced ascites development and tumour burden. BA treatments depleted TGF-Ī² and VEGF in ascites, and skewed the TIME towards cytotoxicity compared to control. In the BR5 HGSC syngeneic model, BA treatments increased tumour-infiltrating CD8 T cells with effector memory and cytotoxic markers, as well as cytolytic NK cells. Extended BA treatments in the BR5 model produced ā¼50% BA-cured mice that were protected from re-challenge. These BA-cured mice had increased peritoneal T-effector memory and NK cells compared to controls. Our preclinical studies of BA in advanced ovarian cancer models support further testing of BA as an improved immunotherapy option for patients with advanced ovarian cancer. Ā© 2024. The Author(s).
- Mus musculus (House mouse),
- Biochemistry and Molecular biology,
- Cancer Research,
- Cell Biology,
- Immunology and Microbiology
Interleukin-21 receptor signaling promotes metabolic dysfunction-associated steatohepatitis-driven hepatocellular carcinoma by inducing immunosuppressive IgA+ B cells.
In Molecular Cancer on 8 May 2024 by Xie, Y., Huang, Y., et al.
Dysregulation of immune surveillance is tightly linked to the development of metabolic dysfunction-associated steatohepatitis (MASH)-driven hepatocellular carcinoma (HCC); however, its underlying mechanisms remain unclear. Herein, we aimed to determine the role of interleukin-21 receptor (IL-21R) in MASH-driven HCC. The clinical significance of IL-21R was assessed in human HCC specimens using immunohistochemistry staining. Furthermore, the expression of IL-21R in mice was assessed in the STAM model. Thereafter, two different MASH-driven HCC mouse models were applied between IL-21R-deficient mice and wild type controls to explore the role of IL-21R in MASH-driven HCC. To further elucidate the potential mechanisms by which IL-21R affected MASH-driven HCC, whole transcriptome sequencing, flow cytometry and adoptive lymphocyte transfer were performed. Finally, flow cytometry, enzyme-linked immunosorbent assay, immunofluorescent staining, chromatin immunoprecipitation assay and western blotting were conducted to explore the mechanism by which IL-21R induced IgA+ B cells. HCC patients with high IL-21R expression exhibited poor relapse-free survival, advanced TNM stage and severe steatosis. Additionally, IL-21R was demonstrated to be upregulated in mouse liver tumors. Particularly, ablation of IL-21R impeded MASH-driven hepatocarcinogenesis with dramatically reduction of lipid accumulation. Moreover, cytotoxic CD8+ T lymphocyte activation was enhanced in the absence of IL-21R due to the reduction of immunosuppressive IgA+ B cells. Mechanistically, the IL-21R-STAT1-c-Jun/c-Fos regulatory axis was activated in MASH-driven HCC and thus promoted the transcription of Igha, resulting in the induction of IgA+ B cells. IL-21R plays a cancer-promoting role by inducing IgA+ B cells in MASH-driven hepatocarcinogenesis. Targeting IL-21R signaling represents a potential therapeutic strategy for cancer therapy. Ā© 2024. The Author(s).
- Mus musculus (House mouse),
- Cardiovascular biology
Stroke and myocardial infarction induce neutrophil extracellular trap release disrupting lymphoid organ structure and immunoglobulin secretion.
In Nat Cardiovasc Res on 1 May 2024 by Tuz, A. A., Ghosh, S., et al.
Post-injury dysfunction of humoral immunity accounts for infections and poor outcomes in cardiovascular diseases. Among immunoglobulins (Ig), IgA, the most abundant mucosal antibody, is produced by plasma B cells in intestinal Peyer's patches (PP) and lamina propria. Here we show that patients with stroke and myocardial ischemia (MI) had strongly reduced IgA blood levels. This was phenocopied in experimental mouse models where decreased plasma and fecal IgA were accompanied by rapid loss of IgA-producing plasma cells in PP and lamina propria. Reduced plasma IgG was detectable in patients and experimental mice 3-10ād after injury. Stroke/MI triggered the release of neutrophil extracellular traps (NETs). Depletion of neutrophils, NET degradation or blockade of NET release inhibited the loss of IgA+ cells and circulating IgA in experimental stroke and MI and in patients with stroke. Our results unveil how tissue-injury-triggered systemic NET release disrupts physiological Ig secretion and how this can be inhibited in patients. Ā© 2024. The Author(s).
- Mus musculus (House mouse),
- Cancer Research,
- Immunology and Microbiology
An immune cell map of human lung adenocarcinoma development reveals an anti-tumoral role of the Tfh-dependent tertiary lymphoid structure.
In Cell Reports Medicine on 19 March 2024 by Liu, W., You, W., et al.
The immune responses during the initiation and invasion stages of human lung adenocarcinoma (LUAD) development are largely unknown. Here, we generated a single-cell RNA sequencing map to decipher the immune dynamics during human LUAD development. We found that T follicular helper (Tfh)-like cells, germinal center B cells, and dysfunctional CD8+ TĀ cells increase during tumor initiation/invasion and form a tertiary lymphoid structure (TLS) inside the tumor. This TLS starts with an aggregation of CD4+ TĀ cells and the generation of CXCL13-expressing Tfh-like cells, followed by an accumulation of B cells, and then forms a CD4+ T and B cell aggregate. TLS and its associated cells are correlated with better patient survival. InhibitingĀ TLS formation by Tfh or B cell depletion promotes tumor growth in mouse models. The anti-tumoralĀ effect of the Tfh-dependent TLS is mediated through interleukin-21 (IL-21)-IL-21 receptor signaling. Our study establishes an anti-tumoral role of the Tfh-dependent TLS in the development of LUAD. Copyright Ā© 2024 The Author(s). Published by Elsevier Inc. All rights reserved.
- Mus musculus (House mouse),
- Immunology and Microbiology
Natural antibodies drive type 2 immunity in response to damage-associated molecular patterns.
In JCI Insight on 12 March 2024 by Mara, A. B., Rawat, K., et al.
PubMed
Allergic airway disease (AAD) is an example of type 2 inflammation that leads to chronic airway eosinophilia controlled by CD4 Th2 cells. Inflammation is reinforced by mast cells and basophils armed with allergen-specific IgE made by allergen-specific B2 B cells of the adaptive immune system. Little is known about how AAD is affected by innate B1 cells, which produce natural antibodies (NAbs) that facilitate apoptotic cell clearance and detect damage- and pathogen-associated molecular patterns (DAMPS and PAMPS). We used transgenic mice lacking either B cells or NAbs in distinct mouse models of AAD that require either DAMPS or PAMPS as the initial trigger for type 2 immunity. In a DAMP-induced allergic model, driven by alum and uric acid, mouse strains lacking B cells (CD19DTA), NAbs (IgHEL MD4), or all secreted antibodies (sIgm-/-Aid-/-) displayed a significant reduction in both eosinophilia and Th2 priming compared with WT or Aid-/- mice lacking only germinal center-dependent high-affinity class-switched antibodies. Replenishing B cell-deficient mice with either unimmunized B1 B cells or NAbs during sensitization restored eosinophilia, suggesting that NAbs are required for licensing antigen-presenting cells to prime type 2 immunity. Conversely, PAMP-dependent type 2 priming to house dust mite or Aspergillus was not dependent on NAbs. This study reveals an underappreciated role of B1 B cell-generated NAbs in selectively driving DAMP-induced type 2 immunity.
- Mus musculus (House mouse),
- Cancer Research,
- Immunology and Microbiology
CMTM6 maintains B cell-intrinsic CD40 expression to regulate anti-tumor immunity
Preprint on BioRxiv : the Preprint Server for Biology on 10 March 2024 by Long, Y., Chen, R., et al.
SUMMARY Tumor cell CMTM6 is a novel tumor immunoregulator involved in maintaining membrane levels of several important molecules, such as PD-L1 and CD58. Host CMTM6 may also play a function in the tumor microenvironment. Here, we found that CMTM6 was highly expressed in splenic B cells and tumor-infiltrating B cells. CMTM6 deficiency resulted in impaired splenic development, germinal center B cell differentiation, memory B cell differentiation, and B cell anti-tumor immune responses. Through multi-omics data mining and B-cell agonist screening, we identified that CMTM6 interacted with CD40 and maintained CD40 membrane levels in B cells. CMTM6 regulated CD40 at the post-translational modification stage but not at the transcriptional stage. CMTM6 deficiency led to impaired CD40 signaling-mediated B cell activation, survival, proliferation, and differentiation. In vivo, CMTM6 deficiency leads to a significant decrease in the anti-tumor activity of B cell-dependent CD40 agonists. Collectively, B-cell intrinsic CMTM6 maintains B cell CD40 levels and signaling to promote B cell function and anti-tumor immunity. Highlights B cells participate in anti-tumor immunity by influencing the intratumoral infiltration and function of T cells; CMTM6 cis-interacts with CD40 to maintain CD40 cell membrane levels; Loss of B cell-intrinsic CMTM6 significantly reduces CD40 signaling-mediated B cell activation, survival, and differentiation; CMTM6 deficiency leads to a significant reduction in the anti-tumor activity of B cells and CD40 agonists. In Brief Long et al. demonstrate that B-cell intrinsic CMTM6 regulates CD40 signaling and function via maintaining the cell membrane level of B-cell CD40 through a post-translational modification pathway, thereby affecting anti-tumor B-cell immunity and the efficacy of CD40 agonist.
- Mus musculus (House mouse)
Dnmt3amutations limit normal and autoreactive Tfh differentiation
Preprint on BioRxiv : the Preprint Server for Biology on 21 February 2024 by Shen, Y., Li, Z., et al.
Rheumatoid arthritis (RA) is an autoimmune disease characterized by joint inflammation, strongly associated with the activity of autoreactive CD4+ T cells. DNMT3A mutations are the most common somatic mutations found in the hematopoietic system of patients with rheumatoid arthritis. However, the role of DNMT3A in CD4+ T cells and CD4+ T follicular helper (Tfh) cells is poorly understood. Since somatic mutations are not identified in standard genome-wide association studies, somatic mutationsā impact on the etiology of diseases could be underestimated. Here, we thoroughly characterized and used the KRN+ splenocyte transfer model of autoimmune joint inflammation and inactivated Dnmt3a using CRISPR-Cas9 and standard Cre/loxP approaches. Experiments with competitive bone marrow (BM) chimeras identified a positive role for Dnmt3a in Tfh differentiation, which was validated by comparing mice with Dnmt3a mutations in CD4+ cells to animals with WT Dnmt3a . In conclusion, We identify that Dnmt3a mutations limit normal and autoreactive Tfh differentiation. Key findings ā Dnmt3a mutations limit Tfh differentiation, which could contribute to reduced immune responses in individuals with somatic DNMT3A mutations. ā Deep characterization of the KRN+ splenocyte transfer model defines a dynamic process leading to reproducible autoimmune joint inflammation. ā The immuno-CRISPR (iCR) methodology can be used to test the role of candidate genes in disease models.
- Mus musculus (House mouse),
- Immunology and Microbiology
Glycosylation-modified antigens as a tolerance-inducing vaccine platform prevent anaphylaxis in a pre-clinical model of food allergy.
In Cell Reports Medicine on 16 January 2024 by Cao, S., Maulloo, C. D., et al.
The only FDA-approved oral immunotherapy for a food allergy provides protection against accidental exposure to peanuts. However, this therapy often causes discomfort or side effects and requires long-term commitment. Better preventive and therapeutic solutions are urgently needed. We develop a tolerance-inducing vaccine technology that utilizes glycosylation-modified antigens to induce antigen-specific non-responsiveness. The glycosylation-modified antigens are administered intravenously (i.v.) or subcutaneously (s.c.) and traffic to the liver or lymph nodes, respectively, leading to preferential internalization by antigen-presenting cells, educating the immune system to respond in an innocuous way. In a mouse model of cow's milk allergy, treatment with glycosylation-modified Ī²-lactoglobulin (BLG) is effective in preventing the onset of allergy. In addition, s.c. administration of glycosylation-modified BLG shows superior safety and potential in treating existing allergies in combination with anti-CD20 co-therapy. This platform provides an antigen-specific immunomodulatory strategy to prevent and treat food allergies. Copyright Ā© 2024 The Authors. Published by Elsevier Inc. All rights reserved.
- Mus musculus (House mouse),
- Cancer Research
Engineer a double team of short-lived and glucose-sensing bacteria for cancer eradication.
In Cell Reports Medicine on 20 June 2023 by Jin, Y. & Fu, L.
PubMed
Rationally designed and engineered bacteria represent an emerging unique approach for cancer treatment. Here, we engineer a short-lived bacterium, mp105, that is effective against diverse cancer types and safe for intravenous administration. We reveal that mp105 combats cancer by direct oncolysis, depletion of tumor-associated macrophages, and elicitation of CD4+ TĀ cell immunity. We further engineer a glucose-sensing bacterium named m6001 that selectively colonizes solid tumors. When intratumorally injected, m6001 clears tumors more efficiently than mp105 due to its post-delivery replication in tumors and potent oncolytic capacity. Finally, we combine intravenous injection of mp105 and intratumoral injection of m6001, forming a double team against cancer. The double team enhances cancer therapy compared with single treatment for subjects carrying both intratumorally injectable and uninjectable tumors. The two anticancer bacteria and their combination are applicable to different scenarios, turning bacterial therapy for cancer into a feasible solution. Copyright Ā© 2023 The Author(s). Published by Elsevier Inc. All rights reserved.
- Cancer Research
Profiling of syngeneic mouse HCC tumor models as a framework to understand anti-PD-1 sensitive tumor microenvironments.
In Hepatology on 1 May 2023 by Zabransky, D. J., Danilova, L., et al.
PubMed
The treatment of hepatocellular carcinoma (HCC) has been transformed by the use of immune checkpoint inhibitors. However, most patients with HCC do not benefit from treatment with immunotherapy. There is an urgent need to understand the mechanisms that underlie response or resistance to immunotherapy for patients with HCC. The use of syngeneic mouse models that closely recapitulate the heterogeneity of human HCC will provide opportunities to examine the complex interactions between cancer cells and nonmalignant cells in the tumor microenvironment. We leverage a multifaceted approach that includes imaging mass cytometry and suspension cytometry by time of flight to profile the tumor microenvironments of the Hep53.4, Hepa 1-6, RIL-175, and TIBx (derivative of TIB-75) syngeneic mouse HCC models. The immune tumor microenvironments vary across these four models, and various immunosuppressive pathways exist at baseline in orthotopic liver tumors derived from these models. For instance, TIBx, which is resistant to anti-programmed cell death protein 1 therapy, contains a high proportion of "M2-like" tumor-associated macrophages with the potential to diminish antitumor immunity. Investigation of The Cancer Genome Atlas reveals that the baseline immunologic profiles of Hep53.4, RIL-175, and TIBx are broadly representative of human HCCs; however, Hepa 1-6 does not recapitulate the immune tumor microenvironment of the vast majority of human HCCs. There is a wide diversity in the immune tumor microenvironments in preclinical models and in human HCC, highlighting the need to use multiple syngeneic HCC models to improve the understanding of how to treat HCC through immune modulation. Copyright Ā© 2023 American Association for the Study of Liver Diseases.
- Cancer Research,
- Immunology and Microbiology
Balance between immunoregulatory B cells and plasma cells drives pancreatic tumor immunity.
In Cell Reports Medicine on 20 September 2022 by Mirlekar, B., Wang, Y., et al.
PubMed
Plasma cell responses are associated with anti-tumor immunity and favorable response to immunotherapy. BĀ cells can amplify anti-tumor immune responses through antibody production; yet B cells in patients and tumor-bearing mice often fail to support this effector function. We identify dysregulated transcriptional program in B cells that disrupts differentiation of naive B cells into anti-tumor plasma cells. The signaling network contributing to this dysfunction is driven by interleukin (IL) 35 stimulation of a STAT3-PAX5 complex that upregulates the transcriptional regulator BCL6 in naive B cells. Transient inhibition of BCL6 in tumor-educated naive B cells is sufficient to reverse the dysfunction in B cell differentiation, stimulating the intra-tumoral accumulation of plasma cells and effector TĀ cells and rendering pancreatic tumors sensitive to anti-programmed cell death protein 1 (PD-1) blockade. Our findings argue that B cell effector dysfunction in cancer can be due to an active systemic suppression program that can be targeted to synergize with TĀ cell-directed immunotherapy. Copyright Ā© 2022 The Authors. Published by Elsevier Inc. All rights reserved.
