Evidence map›Paper›PMID 40673486›Full record

ArticleCancer research communications2025

In Situ Proinflammatory Effects of Dazostinag Alone or with Chemotherapy on the Tumor Microenvironment of Patients with Head and Neck Squamous Cell Carcinoma.

Richard C Gregory, Neil Lineberry, Alex Parent, Karthik Rajasekaran, Thomas J Ow, Cherie-Ann Nathan, Beryl A Hatton, Wendy Jenkins, Marc Grenley, Connor Burns and 5 more

Abstract read
In one paragraph

Article in Cancer research communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

15 authors.

Richard C GregoryTakeda Development Center Americas, Inc. (TDCA), Cambridge, Massachusetts.ORCID 0000-0002-5041-1882
Neil LineberryTakeda Development Center Americas, Inc. (TDCA), Cambridge, Massachusetts.ORCID 0000-0001-9156-4423
Alex ParentTakeda Development Center Americas, Inc. (TDCA), Cambridge, Massachusetts.ORCID 0000-0001-6419-3719
Karthik RajasekaranUniversity of Pennsylvania, Philadelphia, Pennsylvania.ORCID 0000-0003-2148-1643
Thomas J OwAlbert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York.ORCID 0000-0001-9389-2332
Cherie-Ann NathanLouisiana State University Health, Shreveport, Louisiana.ORCID 0000-0001-7386-318X
Beryl A HattonPresage Biosciences, Inc., Seattle, Washington.ORCID 0000-0002-5635-3388
Wendy JenkinsPresage Biosciences, Inc., Seattle, Washington.ORCID 0009-0001-4592-1773
Marc GrenleyPresage Biosciences, Inc., Seattle, Washington.ORCID 0009-0001-0177-7896
Connor BurnsPresage Biosciences, Inc., Seattle, Washington.ORCID 0009-0008-9365-3612
Angela MerrellPresage Biosciences, Inc., Seattle, Washington.ORCID 0009-0008-0899-304X
Jason P FrazierPresage Biosciences, Inc., Seattle, Washington.ORCID 0009-0006-3044-6136
Jonathan M J DerryPresage Biosciences, Inc., Seattle, Washington.ORCID 0009-0005-7620-0003
Emily BeirnePresage Biosciences, Inc., Seattle, Washington.ORCID 0009-0008-3325-082X
Richard A KlinghofferPresage Biosciences, Inc., Seattle, Washington.ORCID 0009-0003-4913-5803

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeThe tumor microenvironment (TME) is difficult to model in an in vivo cancer research setting. This study leveraged intratumor microdosing using comparative in vivo oncology (CIVO) with spatial profiling to evaluate the effects of the stimulator of interferon genes agonist dazostinag, alone or with chemotherapy, on cellular responses within the native TME of intact human tumors. PATIENTS AND

methodsThis phase 0 study enrolled adult patients with head and neck squamous cell carcinoma (HNSCC) planned for surgical intervention. Intratumoral microdose injections of dazostinag (maximum dose: 1.68 μg in a 0.05 mg/mL solution), alone or combined with various chemotherapies, were delivered via CIVO to tumors 24, 48, 72, or 96 hours prior to resection. Each tumor sample was prepared for analysis using IHC and ISH. Analysis of the microdosed tumors using the GeoMx Digital Spatial Profiler and CosMx Spatial Molecular Imager was performed in one patient.

resultsType 1 IFN signaling was induced with dazostinag alone and in combination with chemotherapy from multiple cell types within the TME, including immune cells. Dazostinag also shifted the polarization of macrophages from an immune-suppressive phenotype to a proinflammatory phenotype at 24 hours after injection. Enrichment of cytotoxic T cells was observed in regions of localized dazostinag exposure, coinciding with increased chemokine (CXCL9) expression. Based on cleaved caspase-3, an apoptosis marker, dazostinag plus chemotherapy increased cellular apoptosis relative to either drug alone.

conclusionsUtilizing CIVO and spatial profiling technology, dazostinag alone and combined with chemotherapy promoted an early proinflammatory response and enhanced chemotherapy-mediated cell death in the native TME of intact human HNSCC tumors. SIGNIFICANCE: The CIVO approach demonstrates that dazostinag alone and combined with chemotherapy promotes both proapoptotic and early proinflammatory responses in the native TME of intact human HNSCC tumors, providing clinical evidence for an on-target mechanism of action and rationale for further clinical investigation.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsHead and Neck NeoplasmsSquamous Cell Carcinoma of Head and NeckTumor MicroenvironmentAdultAgedApoptosisFemaleHumansMaleMiddle Aged

Identifiers

PMID40673486
PMCPMC12308172

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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.