.2017 Mar 16;543(7645):428-432.

doi: 10.1038/nature21409. Epub 2017 Mar 8.

Class IIa HDAC inhibition reduces breast tumours and metastases through anti-tumour macrophages

Jennifer L Guerriero¹, Alaba Sotayo¹, Holly E Ponichtera¹, Jessica A Castrillon¹, Alexandra L Pourzia¹, Sara Schad¹, Shawn F Johnson¹, Ruben D Carrasco², Suzan Lazo¹, Roderick T Bronson³, Scott P Davis⁴, Mercedes Lobera⁴, Michael A Nolan⁴, Anthony Letai¹

Affiliations

¹ Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, Massachusetts 02115, USA.
² Department of Pathology, Brigham and Women's Hospital, 75 Francis Street, Massachusetts 02115, USA.
³ Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
⁴ GlaxoSmithKline, 200 Technology Square Suite 602, Cambridge, Massachusetts 02139, USA.

PMID:28273064
PMCID: PMC8170529
DOI: 10.1038/nature21409

Class IIa HDAC inhibition reduces breast tumours and metastases through anti-tumour macrophages

Jennifer L Guerriero et al. Nature.2017.

.2017 Mar 16;543(7645):428-432.

doi: 10.1038/nature21409. Epub 2017 Mar 8.

Authors

Affiliations

¹ Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, Massachusetts 02115, USA.
² Department of Pathology, Brigham and Women's Hospital, 75 Francis Street, Massachusetts 02115, USA.
³ Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
⁴ GlaxoSmithKline, 200 Technology Square Suite 602, Cambridge, Massachusetts 02139, USA.

PMID:28273064
PMCID: PMC8170529
DOI: 10.1038/nature21409

Abstract

Although the main focus of immuno-oncology has been manipulating the adaptive immune system, harnessing both the innate and adaptive arms of the immune system might produce superior tumour reduction and elimination. Tumour-associated macrophages often have net pro-tumour effects, but their embedded location and their untapped potential provide impetus to discover strategies to turn them against tumours. Strategies that deplete (anti-CSF-1 antibodies and CSF-1R inhibition) or stimulate (agonistic anti-CD40 or inhibitory anti-CD47 antibodies) tumour-associated macrophages have had some success. We hypothesized that pharmacologic modulation of macrophage phenotype could produce an anti-tumour effect. We previously reported that a first-in-class selective class IIa histone deacetylase (HDAC) inhibitor, TMP195, influenced human monocyte responses to the colony-stimulating factors CSF-1 and CSF-2 in vitro. Here, we utilize a macrophage-dependent autochthonous mouse model of breast cancer to demonstrate that in vivo TMP195 treatment alters the tumour microenvironment and reduces tumour burden and pulmonary metastases by modulating macrophage phenotypes. TMP195 induces the recruitment and differentiation of highly phagocytic and stimulatory macrophages within tumours. Furthermore, combining TMP195 with chemotherapy regimens or T-cell checkpoint blockade in this model significantly enhances the durability of tumour reduction. These data introduce class IIa HDAC inhibition as a means to harness the anti-tumour potential of macrophages to enhance cancer therapy.

PubMed Disclaimer

Conflict of interest statement

Authors declare competing financial interests.

Figures

**Extended Data Figure 1.. TMP195 modulates CD11b⁺ cells in breast tumors.**
a, Gating strategy for double-sorting tumor cell suspensions. Mononuclear cells gated on the basis of FSC-A vs. SSC-A were sequentially gated to select single cells (FSC-H vs. FSC-W then SSC-H vs. SSC-W). Single cells were then gated to select live CD45⁺ (7-AAD vs CD45). Live CD45⁺ cells were then gated to select CD19⁻ cells (CD19 vs. CD3). Live/CD45⁺/CD19⁻ cells were then gated to select either CD11b⁺ or CD3⁺ cells (CD11b vs. CD3). Tumor suspensions were sorted on a BD Aria II into CD11b+ or CD3⁺ fractions. These fractions were concentrated by centrifugation and sorted through the same gating strategy a second time to increase the purity of each population. The purity of these double-sorted populations were confirmed for each sample prior to RNA isolation. Representative purity checks of the double-sorted CD3⁺**(b)** and CD11b⁺**(c)** populations are shown.d, Mean vs. Expression Value plots of Affymetrix transcriptional profiling data. All probesets are shown, highlights apply only to probesets with a δ-factor >1.5.e-j, Starting with the list of genes most affected by 5-day TMP195 treatment (δ-factor >1.5), we queried their biological processes in the PANTHER GO-Slim gene ontology database and compared that to the distribution of biological processes represented in the genome.e, The genes induced by TMP195 treatment had a significant over- or under-representation of the ontologies illustrated in the pie charts and embedded table of statistics. Unbiased analysis of TMP195-induced differential gene expression through GSEA of all probesets revealed a significant bias (χ2 P value <0.05) in the distribution of the expression values of five gene sets as highlighted on the volcano plots (Y-axis = Student’s t test P value).f-j, Probesets representing genes in both the δ-factor list we selected and the GSEA gene set are labeled with the gene symbol corresponding to that probeset.

**Extended Data Figure 2.. TMP195 induced recruitment of tumor infiltrating leukocytes.**
Tumor bearing MMTV-PyMT mice were randomly placed into treatment groups and received daily intraperitoneal (IP) injections of either vehicle (DMSO) or 50 mg/kg of TMP195 for the indicated days. IHC was performed on tumor sections fora, the myeloid marker, CD11b, andb, the macrophage specific marker, F480. Quantitation as percent of total tissue is shown to the right of each representative section. Vehicle (5 days of DMSO) and 5 day TMP195 quantitation is taken from Figure 1a and 2a for reference. Scale bar represents 100 μm. Significance: t test *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001.c, Negative controls for the CD40 IHC staining (Fig. 2f) are shown. Both rabbit IgG and no primary antibody controls are shown in TMP195 treated tumors and reveal no background or non-specific positive signal.d-p, Whole tumors were processed into single cells and flow cytometry was performed to determine the extent of immune cell infiltration into tumors. Representative graphs are shown from at least 3 independent experiments of 3–5 animals per group. Significance: t test *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001.

**Extended Data Figure 3.. Characterization of recruited TMP195-activated myeloid cells.**
Tumor bearing MMTV-PyMT mice were randomly placed into treatment groups and received daily IP injections of either vehicle (DMSO) or 50 mg/kg of TMP195 for 5 days. Whole tumors were processed into single cells and flow cytometry was performed.a, Gating strategy for MHCII⁺CD11b^lo versus MHCII⁺CD11b^hi.b, Representative MTM vs TAM plots of 5 vehicle treated and 5 TMP195 treated mice with quantitation. Graphs show the results from 5 independent experiments where there were 3–5 animals per treatment group.c-e, To identify pre-existing versus new tumor macrophages, mice were pretreated with dextran labelled with Alexa555, which is ingested by macrophages. Then mice were treated for 5 days with vehicle or TMP195. Mice were injected with dextran labelled with Alexa594 before sacrifice. Whole tumors were processed into single cells and flow cytometry was performed.d, There is an increase in new but not pre-existing macrophages in tumors from TMP195 treated animals. Representative graph from two separate experiments with n=3 per treatment group (unpaired t-test)e, Of note, the new macrophages are MHCII⁺CD11b^hi (MTM). Significance: t test *P<0.05.f, Mice received one IP injection of either vehicle (DMSO) or 50 mg/kg of TMP195. The following day mice were IV injected with CD11b⁺ cells labelled with CFSE. Mice were then treated for an additional 5 days with vehicle or compound.g, Whole tumors were processed into single cells and flow cytometry was performed. Thirteen mice from 3 different experiments are shown. There is a significant increase in recruitment of IV injected CD11b⁺CFSE⁺ monocytes to tumors in TMP195 treated mice. Graphs show the results from 2 independent experiments (unpaired t-test). All graphs show mean and error bars represent S.E.M. Significance: *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001.

**Extended Data Figure 4.. TMP195-activated myeloid cells are highly phagocytic, engulf breast tumor cells and are co-stimulatory.**
Mice were treated for 5 days with vehicle or 50 mg/kg of TMP195. Whole tumors were processed into single cells.a, Flow cytometry was performed and representative flow cytometry plots are shown indicating intracellular EPCAM signal inside F480⁺ macrophages, which corresponds with Figure 2c.b-d, CD11b⁺ cells were isolated from tumors and cytospun onto glass slides. Immunofluorescence was performed to identify phagocytosed breast tumor cells (corresponding with Fig. 2d).e, Representative flow cytometry plots of CD40⁺CD11b⁺ monocytes, and quantitation.f-g, In vitro TMP195 treatment enhances the co-stimulatory activity of monocytes differentiated in IL-4 / GM-CSF. Human monocytes purified from peripheral blood were differentiated with IL-4 and GM-CSF for 5 days in the presence of 300 nM TMP195 or 0.1% DMSO as a control.f, FACS analysis of CD80 and CD86 shows an increase in the proportion of cells expressing the co-stimulatory molecule CD86.g, Following the 5-day differentiation, monocytes were used cells as APCs in a polyclonal T cell proliferation assay (10 CFSE-labeled naïve CD4+ T cells per 1 differentiated monocyte), T cells display a higher degree of proliferation (Division Index, FlowJo, Treestar Inc.) when co-cultured with monocytes differentiated in 300nM TMP195 compared to the DMSO control monocytes. Data is representative of three independent experiments, each with two unique blood donors per experiment. Significance: t test **P<0.01.

**Extended Data Figure 5.. TMP195 is not directly cytotoxic.**
Tumor bearing MMTV-PyMT mice were randomly placed into treatment groups. Mice received daily IP injections of either vehicle (DMSO) for 5 days or 50 mg/kg of TMP195 for 1, 3, or 5 days. IHC was performed on tumor sections fora, a marker of vasculature, CD34,b, a marker of proliferation, Ki67, andd, a marker of apoptosis, cleaved Caspase 3 (CC3). Quantitation as percent of total tissue is shown to the right of each representative section. Vehicle (5 days of DMSO) and 5 day TMP195 quantitation is taken from Figure 2h for reference. For IHC representative quantitation and images are shown from two independent experiments with at least 3 mice per group. Scale bar represents 100 μm. Significance: t test *P<0.05, **P<0.01, ***P<0.001 and ***P<0.0001.c, Whole tissue lysate was used to generate lysates for immunoblotting analysis using markers of apoptosis, Parp and Cleaved caspase 3. Each lane represents an individual tumor. For gel source data, see Supplementary Figure 1.e, Human or mouse breast tumor cells were plated and treated with increasing concentrations of TMP195 (0, 0.1, 1, 10 μM), an inactive isomer, TMP058 (Ref #6; 0, 0.1, 1, 10 μM), Staurosporine (0, 1, 10, 100 ng/mL) or Etoposide (0, 10, 50, 100 μM), for 48 hours. CellTiter-Glo was used to assess cell viability. Error bars represent the average of three independent experiments. Shown in the mean and error bars represent S.E.M. An unpaired t-test was performed for all statistical values.

**Extended Data Figure 6.. TMP195 induces reduction in tumor burden and decreases pulmonary metastasis.**
a, Treatment regimen of three independent experiments testing single agent efficacy of TMP195.b, Mice with total tumor burden between 150–800 mm³ were treated with DMSO (n=12) or 50 mg/kg of TMP195 (n=13) for 13 days. Tumor volume was measured and plotted as total tumor burden ±SEM.c, The mice whose tumors started between 150–400 mm³ were kept on therapy to day 24 (DMSO n=5; TMP195 n=6).d, At day 24 their lungs were removed and H&E was performed to assess pulmonary metastasis. The number of metastatic lesions per lung section is quantitated and the mean is shown ±SEM. Significance: t-test P ***P<0.0001.e,f, Two additional independent experiments were performed to test single agent efficacy of TMP195.

**Extended Data Figure 7.. Two week TMP195 treatment results in the biased distribution of select cell type signatures**
a, Volcano plot of Affymetrix gene expression in RNA isolated from whole tumors (n=3 mice per treatment group) demonstrates an overall lack of differential gene expression in these samples. However, analysis for biased enrichment of the ImmGen cell type signature gene sets identifies only 5 populations of cells as significantly (χ2 P value <0.05) affected by TMP195 treatment as listed in (b) and illustrated in the volcano plots (**c-g**). For a visual point of reference, the unaffected natural killer gene signature is highlighted in volcano ploth. Volcano plot y-axes are Student’s t test P values.

**Extended Data Figure 8.. Macrophages are required for efficacy of TMP195.**
Tumor bearing MMTV-PyMT mice were randomly placed into treatment groups. Mice received daily IP injections of either vehicle (DMSO) or 50 mg/kg of TMP195 in combination with (**a,b and h,i**) a myeloid depleting antibody (α-CD11b) or (**c-g**) a macrophage depleting antibody (α-CSF-1).a, Tumor volumes were measured and plotted as average total tumor burden ±SEM.b, Tumors were removed from animals at the end of the CD11b depletion experiment and IHC was used to confirm the depletion of myeloid cells in the tumor tissue.c-g, Corresponding with Figure 3c, at the end of the experiment, tumors were removed from animals and flow cytometry was used to confirm depletion of macrophages in the tumor tissue.f, MHCII⁺CD11b^hi but not MHCII⁺CD11b^lo macrophage populations were significantly depleted in response to the α-CSF-1 depletion strategy.h,i, Corresponding with Extended Data Fig. 12a, at the end of the experiment, tumors were removed from animals and IHC was used to assessh, cell death andi, cellular proliferation.

**Extended Figure 9.. CD8⁺ but not CD4⁺ T cells are required for optimal TMP195 efficacy.**
a, Wild-type FVB/N andb, immunodeficient athymic nude mice were implanted with tumor chunks from MMTV-PyMT transgenic mice and treated daily for 16 days or 20 days, respectively, with vehicle (DMSO) or 50 mg/kg of TMP195. Athymic nude mice were also treated with paclitaxel (PTX) as a positive control. Tumor burden(a) or relative tumor burden(b) is shown for each mouse. Relative tumor burden is the volume of the tumor at day 0 of treatment compared to indicated day post treatment.c, Tumor bearing MMTV-PyMT mice with similar total tumor burden were randomly placed into treatment groups and received daily IP injections of either vehicle or 50 mg/kg of TMP195 in combination with IgG, α-CD8, α-CD4 or α-IFNγ for 6 days (corresponding with Fig. 3d). At the end of the experiment tumors were removed and single cell suspensions were subjected to flow cytometry to confirm depletion of T cells in the tumor.d,e, Tumor bearing MMTV-PyMT mice with similar total tumor burden were randomly placed into treatment groups and received daily IP injections of either vehicle or 50 mg/kg of TMP195 in combination with IgG or α-CD8 for 14 days.e, CD8⁺ T cell depletion was confirmed by flow cytometry.f, Mice treated with DMSO or TMP195 in combination with isotype or neutralizing anti-IFNγ antibody for 5 days and their tumors were harvested. IHC was performed to identify the extent of vasculature organization.

**Extended Data Figure 10.. Representation of MMTV-PyMT breast tumors with and without TMP195 therapy.**
Breast tumors in MMTV-PyMT transgenic mice contain leaky vasculature and monocytes and pro-tumor macrophages that suppress the function of CD8 T cells (left). Upon treatment with TMP195 (right side), tumor macrophages become activated, expressing CD40, and are highly phagocytic (engulfment of tumor cells depicted). CD8⁺ T cells become Granzyme B⁺ indicating their ability to kill tumor cells. Tumor vasculature becomes more organized and less leaky. Additionally, there is a reduction in tumor volume.

**Figure 1.. TMP195 modulates macrophages in breast tumors.**
a, Heatmap of MMC2 values indicating recombinant HDAC7 catalytic domain (a. a. 483–903) binding to immobilized histone H4 peptides containing the indicated modifications with DMSO or with increasing concentrations of TMP195.b-d, Mice were treated for 5 days as indicated.b, Volcano plots of gene expression datasets derived from FACS double-sorted tumor infiltrating leukocytes. All probesets are shown, highlight coloring applied to differentially expressed (δ-factor >1.5) probeset listed in the heatmap adjacent to each plot.c-d, Tumors were obtained for immunohistochemistry (IHC) forc, the myeloid marker, CD11b andd, the mature macrophage marker, Mac-2 to assess infiltration of monocytes and macrophages. Representative quantitation and images are shown from two separate experiments with at least 5 mice per group. Scale bar represents 100 μm. Graphs show the results from two independent experiments (unpaired t-test). Graphs show mean and error bars represent S.E.M. Significance: **P<0.01, ****P<0.0001.

**Figure 2.. TMP195-activated myeloid cells are highly phagocytic and induce vasculature normalization in breast tumors.**
Mice were treated for 5 days as indicated. IHC was performed using(a) the macrophage specific markers, F480 to identify tingible body macrophages (TBM), indicated by black arrow heads and(b) Cleaved caspase-3 to identify apoptotic bodies within macrophages. Phagocytosis of breast tumor cells was quantified as the proportion of F480⁺ macrophages that contain intracellular EPCAM, a marker of breast tumor cells, by(c) flow cytometry(d) immunofluorescence. The proportion of activated macrophages was identified by(e) flow cytometry using F480⁺CD40⁺ of the CD45⁺MHCII⁺ population of cells.f, IHC was performed to identify CD40⁺ cells.g, The proportion of CD45⁺CD3⁺CD8⁺ cells that are Granzyme B⁺ were identified by flow cytometry. Results from 3 independent experiments are shown. Vascular density and integrity was assessed by(h) IHC using the endothelial cell marker CD34 and(i) by immunofluorescence utilizing localization of IV injected dextran. Graphs show the results from two independent experiments (unpaired t-test). All graphs show mean and error bars represent S.E.M. Significance: *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001.

**Figure 3.. TMP195 induces macrophage-dependent reduction in tumor burden and decreases pulmonary metastasis.**
Tumor bearing MMTV-PyMT mice were randomly placed into treatment groups and received daily IP injections of either vehicle or 50 mg/kg of TMP195, as shown. Tumors were measured and plotted as average total tumor burden ±SEM.a, Three independent experiments are shown, the number of mice per group shown in Extended Data Fig. 6.b, After 14 days of treatment lungs were removed and hematoxylin and eosin (H&E) staining was performed to identify metastatic lesions. Representative sections from two vehicle and two TMP195 treated mice are shown. The number of metastatic lesions per lung is shown. Scale bar represents 100 μm.c, An antibody against CSF-1 was used to deplete macrophages. One mouse died due to unrelated experimental reasons in the TMP195+anti-CSF1 group and is indicated on the graph.d-f, CD8 or CD4 cells were depleted, or IFNγ was neutralized, as indicated.d, Relative tumor burden is shown.e, The proportion of CD45⁺CD3⁺CD8⁺ cells that are Granzyme B⁺ were identified by flow cytometry and(f) IHC was performed using CD34 to measure vascular organization on the indicated mice shown in(d), see images in Extended Data Fig. 9f. Statistics for all mouse experiments were performed using 2-way ANOVA. An unpaired t-test was performed for bar graphs. Significance: *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001.

**Figure 4.. TMP195 improves the efficacy of chemotherapy and checkpoint blockade, and induces a durable response.**
Tumor bearing MMTV-PyMT mice with similar total tumor burden were randomly placed into treatment groups and treated as indicated. Tumor volumes were measured and plotted as either average total tumor burden or relative tumor burden to day 0 of treatment.a, Mice received IP injections of either vehicle (DMSO) or 50 mg/kg of TMP195 in combination with either IV injections of vehicle (Dex₅Water) or 50 mg/kg of carboplatin (Carbo).b, Mice received daily IP injections of either vehicle (DMSO) or 50 mg/kg of TMP195 alone or in combination with IV injections of 10 mg/kg of paclitaxel (PTX).c-d, Mice received daily IP injections of either DMSO or 50 mg/kg of TMP195 alone or in combination with IP injections of 250 μg of anti-PD-1.d, The total tumor burden at day 21 compared to the DMSO control is plotted. Statistics represent unpaired student t-test. Mice that died due to unrelated experimental reasons are indicated on the graph. Significance: *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001. Statistics for all mouse experiments were performed using 2-way ANOVA. Error bars represent S.E.M.

See this image and copyright information in PMC

Comment in

Anticancer therapy: Re-educating macrophages.
Villanueva MT.Villanueva MT.Nat Rev Drug Discov. 2017 Apr 28;16(5):313. doi: 10.1038/nrd.2017.82.Nat Rev Drug Discov. 2017.PMID:28450718No abstract available.
Harnessing class II histone deacetylases in macrophages to combat breast cancer.
Reichman H, Munitz A.Reichman H, et al.Cell Mol Immunol. 2017 Jul;14(7):575-577. doi: 10.1038/cmi.2017.32. Epub 2017 May 29.Cell Mol Immunol. 2017.PMID:28552905Free PMC article.No abstract available.

Cited by

Leveraging microenvironmental synthetic lethalities to treat cancer.
Metcalf KJ, Alazzeh A, Werb Z, Weaver VM.Metcalf KJ, et al.J Clin Invest. 2021 Mar 15;131(6):e143765. doi: 10.1172/JCI143765.J Clin Invest. 2021.PMID:33720045Free PMC article.Review.
Epigenetic Profiling ofPTPN11 Mutant JMML Hematopoietic Stem and Progenitor Cells Reveals an Aberrant Histone Landscape.
Sinha R, Dvorak M, Ganesan A, Kalesinskas L, Niemeyer CM, Flotho C, Sakamoto KM, Lacayo N, Patil RV, Perriman R, Cepika AM, Liu YL, Kuo A, Utz PJ, Khatri P, Bertaina A.Sinha R, et al.Cancers (Basel). 2023 Oct 29;15(21):5204. doi: 10.3390/cancers15215204.Cancers (Basel). 2023.PMID:37958378Free PMC article.
An update to experimental and clinical aspects of tumor-associated macrophages in cancer development: hopes and pitfalls.
Salmaninejad A, Layeghi SM, Falakian Z, Golestani S, Kobravi S, Talebi S, Yousefi M.Salmaninejad A, et al.Clin Exp Med. 2024 Jul 13;24(1):156. doi: 10.1007/s10238-024-01417-w.Clin Exp Med. 2024.PMID:39003350Free PMC article.Review.
Targeting monoamine oxidase A-regulated tumor-associated macrophage polarization for cancer immunotherapy.
Wang YC, Wang X, Yu J, Ma F, Li Z, Zhou Y, Zeng S, Ma X, Li YR, Neal A, Huang J, To A, Clarke N, Memarzadeh S, Pellegrini M, Yang L.Wang YC, et al.Nat Commun. 2021 Jun 10;12(1):3530. doi: 10.1038/s41467-021-23164-2.Nat Commun. 2021.PMID:34112755Free PMC article.
Targeted delivery of miR-99b reprograms tumor-associated macrophage phenotype leading to tumor regression.
Wang L, Hu YY, Zhao JL, Huang F, Liang SQ, Dong L, Chen Y, Yu HC, Bai J, Yang JM, Fan JY, Feng L, Li SZ, Han H, Qin HY.Wang L, et al.J Immunother Cancer. 2020 Sep;8(2):e000517. doi: 10.1136/jitc-2019-000517.J Immunother Cancer. 2020.PMID:32948650Free PMC article.

See all "Cited by" articles

References

1. Pollard JW Tumour-educated macrophages promote tumour progression and metastasis. Nat Rev Cancer 4, 71–78, 10.1038/nrc1256 (2004). - DOI - PubMed
1. DeNardo DG, Brennan DJ, Rexhepaj E, Ruffell B, Shiao SL, Madden SF, Gallagher WM, Wadhwani N, Keil SD, Junaid SA, Rugo HS, Hwang ES, Jirström K, West BL & Coussens LM Leukocyte Complexity Predicts Breast Cancer Survival and Functionally Regulates Response to Chemotherapy. Cancer Discovery 1, 54–67, 10.1158/2159-8274.cd-10-0028 (2011). - DOI - PMC - PubMed
1. Pyonteck SM, Akkari L, Schuhmacher AJ, Bowman RL, Sevenich L, Quail DF, Olson OC, Quick ML, Huse JT, Teijeiro V, Setty M, Leslie CS, Oei Y, Pedraza A, Zhang J, Brennan CW, Sutton JC, Holland EC, Daniel D & Joyce JA CSF-1R inhibition alters macrophage polarization and blocks glioma progression. Nature medicine 19, 1264–1272, 10.1038/nm.3337 (2013). - DOI - PMC - PubMed
1. Beatty GL, Chiorean EG, Fishman MP, Saboury B, Teitelbaum UR, Sun W, Huhn RD, Song W, Li D, Sharp LL, Torigian DA, O’Dwyer PJ & Vonderheide RH CD40 agonists alter tumor stroma and show efficacy against pancreatic carcinoma in mice and humans. Science 331, 1612–1616, 331/6024/1612 [pii] 10.1126/science.1198443 (2011). - DOI - PMC - PubMed
1. Willingham SB, Volkmer JP, Gentles AJ, Sahoo D, Dalerba P, Mitra SS, Wang J, Contreras-Trujillo H, Martin R, Cohen JD, Lovelace P, Scheeren FA, Chao MP, Weiskopf K, Tang C, Volkmer AK, Naik TJ, Storm TA, Mosley AR, Edris B, Schmid SM, Sun CK, Chua MS, Murillo O, Rajendran P, Cha AC, Chin RK, Kim D, Adorno M, Raveh T, Tseng D, Jaiswal S, Enger PO, Steinberg GK, Li G, So SK, Majeti R, Harsh GR, van de Rijn M, Teng NN, Sunwoo JB, Alizadeh AA, Clarke MF & Weissman IL The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors. Proc Natl Acad Sci U S A 109, 6662–6667, 10.1073/pnas.1121623109 (2012). - DOI - PMC - PubMed

Publication types

Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions
Actions
Actions

Related information

Grants and funding

LinkOut - more resources

Full Text Sources
Other Literature Sources
- The Lens - Patent Citations Database
- scite Smart Citations
Medical
- MedlinePlus Health Information
Molecular Biology Databases
- Mouse Genome Informatics (MGI)
- NIAID Data Ecosystem - Find datasets on Infectious and Immune-mediated Diseases
Research Materials
- NCI CPTC Antibody Characterization Program
Miscellaneous
- NCI CPTAC Assay Portal

Movatterモバイル変換

Account

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Full text links

Actions

Share

Class IIa HDAC inhibition reduces breast tumours and metastases through anti-tumour macrophages

Affiliations

Class IIa HDAC inhibition reduces breast tumours and metastases through anti-tumour macrophages

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

Comment in

Similar articles

Cited by

References

Publication types

MeSH terms

Substances

Related information

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical

Molecular Biology Databases

Research Materials

Miscellaneous