Journal: Journal for Immunotherapy of Cancer

Article Title: Combination of gemcitabine and anti-PD-1 antibody enhances the anticancer effect of M1 macrophages and the Th1 response in a murine model of pancreatic cancer liver metastasis

doi: 10.1136/jitc-2020-001367

Figure Lengend Snippet: The response in pancreatic ductular adenocarcinoma (PDAC) liver metastasis tumors of mice treated with gemcitabine (GEM) and anti-programmed cell death 1 (anti-PD-1) Ab. (A) Experimental schedule showing the treatments for PDAC liver metastasis mice: no treatment (phosphate-buffered saline), anti-PD-1 Ab, GEM, and GEM plus anti-PD-1 Ab. Treatment was administered twice a week from day 7 to day 33. Tumor tissues were obtained and stained immunohistochemically on day 34 (n=3 per group). (B) Number of liver metastasis tumor nodules and averaged nodule volumes and (C) macroscopic images of tumors are shown; (B) bars represent mean±SEM; Student’s t-test was performed as statistical analysis. (D) Immunohistochemical analysis of tumors for CD8a+, CD4+, and CD11b+ inflammatory cells. Magnification: ×200; bars: 100 µm. Quantification of cell infiltration by using ImageJ (each area analyzed=1.576 mm 2 , three different areas were analyzed for each sample). White bar: no treatment; light gray bar: anti-PD-1 Ab; dark gray bar: GEM; black bar: GEM plus anti-PD-1 Ab; bars represent mean±SEM; one-way analysis of variance followed by Tukey’s HSD post hoc test was performed as statistical analysis; *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001. DAB, 3,3'-diaminobenzidine; HSD, honestly significant difference.

Article Snippet: The PDAC mice were treated with 50 mg/kg GEM (G0367; TCI, Tokyo, Japan) by tail vein injection, and with or without intraperitoneal injection of anti-PD-1 Ab (200 µg; clone: J43; BD Biosciences, Franklin Lakes, New Jersey) or anti-CD8 Ab (200 µg; clone: 53–6.7; BD Biosciences).

Techniques: Staining, Immunohistochemical staining

Journal: Journal for Immunotherapy of Cancer

Article Title: Combination of gemcitabine and anti-PD-1 antibody enhances the anticancer effect of M1 macrophages and the Th1 response in a murine model of pancreatic cancer liver metastasis

doi: 10.1136/jitc-2020-001367

Figure Lengend Snippet: Gene expression analysis of tumor-infiltrating inflammatory cells (TICs) from pancreatic ductular adenocarcinoma (PDAC) liver metastasis model mice by qRT-PCR. PDAC liver metastasis mice received a single dose of the indicated treatment on day 28 and tumor tissues were obtained 2 days later for TIC isolation, followed by RNA extraction. Quantitative RT-PCR showing the expression of M1 macrophage-related cytokine genes ( Il6 , Il12a , Il12b , Il1b , and Tnf ), M2 macrophage-related genes ( Arg1 , Il10 , Tgfb1 , and Mmp9 ), proinflammatory chemokines ( Cxcl10 and Ccl2 ), and T-cell activation markers ( Pdcd1 and Prf1 ); n=3; bars represent mean±SEM; Student’s t-test was used for statistical analysis; *p<0.05, **p<0.01. GEM, gemcitabine; PD-1, programmed cell death 1; qRT-PCR, quantitative real-time polymerase chain reaction.

Article Snippet: The PDAC mice were treated with 50 mg/kg GEM (G0367; TCI, Tokyo, Japan) by tail vein injection, and with or without intraperitoneal injection of anti-PD-1 Ab (200 µg; clone: J43; BD Biosciences, Franklin Lakes, New Jersey) or anti-CD8 Ab (200 µg; clone: 53–6.7; BD Biosciences).

Techniques: Expressing, Quantitative RT-PCR, Isolation, RNA Extraction, Activation Assay, Real-time Polymerase Chain Reaction

Journal: Journal for Immunotherapy of Cancer

Article Title: Combination of gemcitabine and anti-PD-1 antibody enhances the anticancer effect of M1 macrophages and the Th1 response in a murine model of pancreatic cancer liver metastasis

doi: 10.1136/jitc-2020-001367

Figure Lengend Snippet: Flow cytometry (FCM) analysis of tumor-infiltrating inflammatory cells (TICs) for lymphoid-lineage cells. Pancreatic ductular adenocarcinoma liver metastasis mice received a single dose of the indicated treatment on day 28 and tumor tissues were obtained 2 days later for TIC isolation followed by FCM analysis; n=3. (A) CD4+ and CD8a+ cells within TICs. (B) Th1 CD4+ cells expressing T-bet and interferon (IFN)-γ; IFN-γ-secreting cells within CD8+ TICs. (C) Regulatory T cell phenotype, CD4+CD25+FoxP3+ cells, and interleukin (IL)-10+-producing cells within Treg cells. (A–C) Bars represent mean±SEM; one-way analysis of variance followed by Tukey’s HSD post hoc test was performed as statistical analysis; *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001. GEM, gemcitabine. PD-1, programmed cell death 1.

Article Snippet: The PDAC mice were treated with 50 mg/kg GEM (G0367; TCI, Tokyo, Japan) by tail vein injection, and with or without intraperitoneal injection of anti-PD-1 Ab (200 µg; clone: J43; BD Biosciences, Franklin Lakes, New Jersey) or anti-CD8 Ab (200 µg; clone: 53–6.7; BD Biosciences).

Techniques: Flow Cytometry, Isolation, Expressing

Journal: Journal for Immunotherapy of Cancer

Article Title: Combination of gemcitabine and anti-PD-1 antibody enhances the anticancer effect of M1 macrophages and the Th1 response in a murine model of pancreatic cancer liver metastasis

doi: 10.1136/jitc-2020-001367

Figure Lengend Snippet: Immunohistochemical analysis of pancreatic ductular adenocarcinoma liver metastasis tumors for myeloid-lineage cells. Treatments were conducted twice a week from day 7 to day 33; tumors were obtained on day 34 and immunohistochemically analyzed for (A) F4/80+, Ly6C+, and Ly6G+, and (B) CD86+, CD206+ infiltrating cells, and programmed cell death-ligand 1 (PD-L1)+ for the indicated treatment. Magnification: ×200; bars: 100 µm. (A, B) Quantification of cell infiltration by using ImageJ (each area analyzed=1.576 mm 2 , 3 different areas were analyzed for each sample). White bar: no treatment; light gray bar: anti-PD-1 Ab; dark gray bar: gemcitabine (GEM); black bar: GEM plus anti-PD-1 Ab. Bars represent mean±SEM; one-way analysis of variance followed by Tukey’s HSD post hoc test was performed as statistical analysis; *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001.

Article Snippet: The PDAC mice were treated with 50 mg/kg GEM (G0367; TCI, Tokyo, Japan) by tail vein injection, and with or without intraperitoneal injection of anti-PD-1 Ab (200 µg; clone: J43; BD Biosciences, Franklin Lakes, New Jersey) or anti-CD8 Ab (200 µg; clone: 53–6.7; BD Biosciences).

Techniques: Immunohistochemical staining

Journal: Journal for Immunotherapy of Cancer

Article Title: Combination of gemcitabine and anti-PD-1 antibody enhances the anticancer effect of M1 macrophages and the Th1 response in a murine model of pancreatic cancer liver metastasis

doi: 10.1136/jitc-2020-001367

Figure Lengend Snippet: Flow cytometry (FCM) analysis of tumor-infiltrating inflammatory cells (TICs) for myeloid-lineage cells. Pancreatic ductular adenocarcinoma liver metastasis mice received the following treatments: no treatment, anti-programmed cell death 1 (anti-PD-1) Ab, gemcitabine (GEM), or GEM plus anti-PD-1 Ab on day 28 and tumor tissues were obtained 2 days later for TIC isolation and FCM; n=3, bars represent mean±SEM. The following cell populations were analyzed: Ly6C+Ly6G− inflammatory monocytes within CD11b+F4/80+ TICs, CD206− M1 macrophages within CD11b+F4/80 high TICs, and CD206+ M2 macrophages within CD11b+F4/80 high TICs. One-way analysis of variance followed by Tukey’s HSD post hoc test was performed as statistical analysis; *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001.

Article Snippet: The PDAC mice were treated with 50 mg/kg GEM (G0367; TCI, Tokyo, Japan) by tail vein injection, and with or without intraperitoneal injection of anti-PD-1 Ab (200 µg; clone: J43; BD Biosciences, Franklin Lakes, New Jersey) or anti-CD8 Ab (200 µg; clone: 53–6.7; BD Biosciences).

Techniques: Flow Cytometry, Isolation

Journal: Journal for Immunotherapy of Cancer

Article Title: Combination of gemcitabine and anti-PD-1 antibody enhances the anticancer effect of M1 macrophages and the Th1 response in a murine model of pancreatic cancer liver metastasis

doi: 10.1136/jitc-2020-001367

Figure Lengend Snippet: Survival of pancreatic ductular adenocarcinoma (PDAC) liver metastasis model mice that underwent treatment. (A) Experimental schedule showing treatment timing: the PDAC liver metastasis mice received treatment 10 times, twice a week from day 7 to day 39, and survival percentage was monitored until day 72. (B) Survival curves of PDAC liver metastasis mice that received: no treatment (only phosphate-buffered saline; n=7), anti-programmed cell death 1 (anti-PD-1) Ab (n=12), gemcitabine (GEM) (n=7), GEM plus anti-PD-1 Ab (n=6), or GEM plus anti-PD-1 Ab plus anti-CD8 Ab (n=7). The log-rank test was performed to obtain the p values: no treatment/anti-PD-1 Ab=0.492723; no treatment/GEM=0.000172; no treatment/GEM plus anti-PD-1 Ab=0.000446; anti-PD-1 Ab/GEM=0.000034; anti-PD-1 Ab/GEM plus anti-PD-1 Ab=0.000098; GEM/GEM plus anti-PD-1 Ab=0.034672; and GEM plus anti-PD-1 Ab/GEM plus anti-PD-1 Ab plus anti-CD8 Ab=0.0345.

Article Snippet: The PDAC mice were treated with 50 mg/kg GEM (G0367; TCI, Tokyo, Japan) by tail vein injection, and with or without intraperitoneal injection of anti-PD-1 Ab (200 µg; clone: J43; BD Biosciences, Franklin Lakes, New Jersey) or anti-CD8 Ab (200 µg; clone: 53–6.7; BD Biosciences).

Techniques:

Journal: Journal for Immunotherapy of Cancer

Article Title: Combination of gemcitabine and anti-PD-1 antibody enhances the anticancer effect of M1 macrophages and the Th1 response in a murine model of pancreatic cancer liver metastasis

doi: 10.1136/jitc-2020-001367

Figure Lengend Snippet: In vitro macrophage polarization assay. Pancreatic ductular adenocarcinoma liver metastasis mice received a single dose of the indicated treatment on day 28 and splenocytes were obtained on day 30. The splenocytes were activated by coculture with irradiated PAN02 cells; after 7 days, activated splenocytes were harvested and cocultured with bone marrow-derived macrophages. After 48 hours, macrophages were collected for (A) flow cytometry analysis of CD11b, CD86, and CD206; and total RNA was isolated for qRT-PCR analysis of (B) Il6 , Il12a , Il1b , and Tnf (M1 macrophage-related genes) or (C) Arg1 , Il10 , Tgfb1 , and Mmp9 (M2 macrophage-related genes). (A–C) n=3; bars represent mean±SEM; Student’s t-test was performed for statistical analysis; *p<0.05, **p<0.01, ***p<0.001. GEM, gemcitabine; PD-1, programmed cell death 1.

Article Snippet: The PDAC mice were treated with 50 mg/kg GEM (G0367; TCI, Tokyo, Japan) by tail vein injection, and with or without intraperitoneal injection of anti-PD-1 Ab (200 µg; clone: J43; BD Biosciences, Franklin Lakes, New Jersey) or anti-CD8 Ab (200 µg; clone: 53–6.7; BD Biosciences).

Techniques: In Vitro, Irradiation, Derivative Assay, Flow Cytometry, Isolation, Quantitative RT-PCR

Journal: Cancer Management and Research

Article Title: Epigenome-Driven Strategies for Personalized Cancer Immunotherapy

doi: 10.2147/CMAR.S272031

Figure Lengend Snippet: Some Immunotherapy Treatments, Their Associated Epigenetic Hallmarks Found in Cancer Patients and Clinical Outcomes

Article Snippet: NSCLC , Use of anti-PD-1 monoclonal Ab , FOXP1 demethylation and EPIMMUNE epigenetic signature , Clinical benefit with PD-1 blockade , [ ] .

Techniques: Methylation, Disruption, Activity Assay

Journal: Cancers

Article Title: Protein Expression in Metastatic Melanoma and the Link to Disease Presentation in a Range of Tumor Phenotypes

doi: 10.3390/cancers12030767

Figure Lengend Snippet: Combinative treatments for metastatic melanoma.

Article Snippet: , Anti PD-1 ab (from BioXCell) LBH589 (HDACi) , Slower tumor progression and increased survival compared with control and single treatments in B16F10 mice model , [ ] .

Techniques: Control

Journal: International Journal of Molecular Sciences

Article Title: Purinergic Signaling in Pancreas—From Physiology to Therapeutic Strategies in Pancreatic Cancer

doi: 10.3390/ijms21228781

Figure Lengend Snippet: Clinical trials (from NIH and EU registers) testing the potential use of purinergic targets in pancreatic and other cancers. Purpose of the studies varies from feasibility to safety, tolerability, pharmacokinetics, immunogenicity, and anti-tumor activity.

Article Snippet: CD73 +/− A2A , CPI-006 (anti-CD73 Ab) +/− ciforadenant (oral A2A inhibitor) +/− pembrolizumab (anti-PD1 Ab) , Corvus Pharmaceuticals , Patients with selected advanced cancers including pancreatic cancer , NCT03454451 , Phase I/Ib.

Techniques: Clinical Proteomics, Drug discovery, Immunopeptidomics, Activity Assay, Biomarker Discovery, Ointment

Journal: Hematology: the American Society of Hematology Education Program

Article Title: Chimeric antigen receptor T cells for mature B-cell lymphoma and Burkitt lymphoma

doi: 10.1182/hematology.2020000133

Figure Lengend Snippet: Actively recruiting CAR T-cell trials for relapsed B-cell lymphomas using tumor antigen targets other than CD19

Article Snippet: Dual target: CD19/CD22 + anti-PD1 Ab , {"type":"clinical-trial","attrs":{"text":"NCT03287817","term_id":"NCT03287817"}} NCT03287817 , Autolus Therapeutics , ≥18 , 1/2 , Y (55% CR) Osborne, 2020 46.

Techniques: