Evidence map›Paper›PMID 33188035›Full record

ArticleJournal for immunotherapy of cancer2020

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.

Tuyen Thuy Bich Ho, Alessandro Nasti, Akihiro Seki, Takuya Komura, Hiiro Inui, Takashi Kozaka, Yoji Kitamura, Kazuhiro Shiba, Taro Yamashita, Tatsuya Yamashita and 6 more

Open access · goldAbstract read
In one paragraph

Article in Journal for immunotherapy of cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
77citing papers in PubMed, 3 pooled it
4.9field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

77 citing papers in PubMed, 3 syntheses or guidelines pooled it, 106 citations in OpenAlex.

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17 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 3 institutions in 1 country.

Tuyen Thuy Bich Ho *Department of Gastroenterology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan.ORCID 0000-0002-5161-338X
Alessandro Nasti *System Biology, Graduate School of Advanced Preventive Medical Sciences, Kanazawa University, Kanazawa, Japan.ORCID 0000-0003-2550-2317
Akihiro SekiDepartment of Gastroenterology, Kanazawa University Hospital, Kanazawa, Japan.
Takuya KomuraDepartment of Gastroenterology, National Hospital Organization Kanazawa Medical Center, Kanazawa, Japan.
Hiiro InuiDepartment of Gastroenterology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan.
Takashi KozakaDivision of Tracer Kinetics, Advanced Science Research Center, Kanazawa University, Kanazawa, Japan.
Yoji KitamuraDivision of Tracer Kinetics, Advanced Science Research Center, Kanazawa University, Kanazawa, Japan.
Kazuhiro ShibaDivision of Tracer Kinetics, Advanced Science Research Center, Kanazawa University, Kanazawa, Japan.
Taro YamashitaDepartment of General Medicine, Kanazawa University Hospital, Kanazawa, Japan.
Tatsuya YamashitaDepartment of Gastroenterology, Kanazawa University Hospital, Kanazawa, Japan.
Eishiro MizukoshiDepartment of Gastroenterology, Kanazawa University Hospital, Kanazawa, Japan.
Kazunori KawaguchiDepartment of Gastroenterology, Kanazawa University Hospital, Kanazawa, Japan.
Takashi WadaDepartment of Nephrology and Laboratory Medicine, Kanazawa University, Kanazawa, Japan.
Masao HondaDepartment of Gastroenterology, Kanazawa University Hospital, Kanazawa, Japan.
Shuichi KanekoDepartment of Gastroenterology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan.
Yoshio SakaiDepartment of Gastroenterology, Kanazawa University Hospital, Kanazawa, Japan yoshios@m-kanazawa.jp.
Kanazawa University · JPKanazawa University Hospital · JPKanazawa Medical Center · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPancreatic ductular adenocarcinoma (PDAC) is among the most dreadful of malignancies, in part due to the lack of efficacious chemotherapy. Immune checkpoint inhibitors, including anti-programmed cell death 1 (anti-PD-1) antibodies, are novel promising forms of systemic immunotherapy. In the current study, we assessed whether gemcitabine (GEM) combined with anti-PD-1 antibody treatment was efficacious as immunochemotherapy for advanced PDAC using a murine model of liver metastasis.

methodsThe murine model of PDAC liver metastasis was established by intrasplenically injecting the murine pancreatic cancer cell line PAN02 into immunocompetent C57BL/6J mice. The mice were treated with an anti-PD-1 antibody, GEM, or a combination of GEM plus anti-PD-1 antibody, and compared with no treatment (control); liver metastases, immune cell infiltration, gene expression, immune cell response phenotypes, and overall survival were investigated.

resultsIn the metastatic tumor tissues of mice treated with GEM plus anti-PD-1 antibody, we observed the increased infiltration of Th1 lymphocytes and M1 macrophages. Gene expression profile analysis of peripheral blood cells obtained from mice treated with GEM plus anti-PD-1 antibody clearly highlighted T cell and innate immune signaling pathways. Survival of PDAC liver metastasis mice was significantly prolonged by the combination therapy (median survival, 66 days) when compared with that of GEM alone treatment (median survival, 56 days). Expanded lymphocytes, which were isolated from the splenocytes of PDAC liver metastasis mice treated with GEM plus anti-PD-1 antibody, had an increased number of M1 macrophages.

conclusionThe combination of anti-PD-1 antibody immunotherapy with GEM was beneficial to treat a murine model of PDAC liver metastasis by enhancing the immune response mediated by Th1 lymphocytes and M1 macrophages and was associated with CD8+ T cells.

Indexed as

AnimalsAntimetabolites, AntineoplasticAntineoplastic Combined Chemotherapy ProtocolsDeoxycytidineDisease Models, AnimalGemcitabineHumansImmune Checkpoint InhibitorsLiver NeoplasmsMacrophagesMiceNeoplasm MetastasisPancreatic NeoplasmsTumor MicroenvironmentAntimetabolites, AntineoplasticDeoxycytidineGemcitabineImmune Checkpoint Inhibitorscombinationdrug therapyimmunityimmunotherapymacrophagestumor microenvironment

Identifiers

PMID33188035
PMCPMC7668383
OpenAlexW3098370510

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.