Evidence map›Paper›PMID 35250995›Full record

ArticleFrontiers in immunology2022

Repolarization of Tumor-Infiltrating Myeloid Cells for Augmentation of CAR T Cell Therapies.

Weichuan Luo, John V Napoleon, Fenghua Zhang, Yong Gu Lee, Bingbing Wang, Karson S Putt, Philip S Low

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Frontiers in immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
3.1field-weighted citation impact, top 7% 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

24 citing papers in PubMed, 31 citations in OpenAlex.

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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

7 authors at 1 institution in 1 country.

Weichuan LuoDepartment of Chemistry, Purdue Institute for Drug Discovery and Purdue Center for Cancer Research, Purdue University, West Lafayette, IN, United States.
John V NapoleonDepartment of Chemistry, Purdue Institute for Drug Discovery and Purdue Center for Cancer Research, Purdue University, West Lafayette, IN, United States.
Fenghua ZhangDepartment of Chemistry, Purdue Institute for Drug Discovery and Purdue Center for Cancer Research, Purdue University, West Lafayette, IN, United States.
Yong Gu LeeDepartment of Chemistry, Purdue Institute for Drug Discovery and Purdue Center for Cancer Research, Purdue University, West Lafayette, IN, United States.
Bingbing WangDepartment of Chemistry, Purdue Institute for Drug Discovery and Purdue Center for Cancer Research, Purdue University, West Lafayette, IN, United States.
Karson S PuttDepartment of Chemistry, Purdue Institute for Drug Discovery and Purdue Center for Cancer Research, Purdue University, West Lafayette, IN, United States.
Philip S LowDepartment of Chemistry, Purdue Institute for Drug Discovery and Purdue Center for Cancer Research, Purdue University, West Lafayette, IN, United States.
Purdue University West Lafayette · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Although CAR T cell therapies have proven to be effective in treating hematopoietic cancers, their abilities to regress solid tumors have been less encouraging. Mechanisms to explain these disparities have focused primarily on differences in cancer cell heterogeneity, barriers to CAR T cell penetration of solid tumors, and immunosuppressive microenvironments. To evaluate the contributions of immunosuppressive tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs) on CAR T cell efficacies, we have exploited the ability of a folate-targeted Toll-like receptor 7 agonist (FA-TLR7-1A) to specifically reactivate TAMs and MDSCs from an immunosuppressive to pro-inflammatory phenotype without altering the properties of other immune cells. We report here that FA-TLR7-1A significantly augments standard CAR T cell therapies of 4T1 solid tumors in immune competent mice. We further show that co-administration of the FA-TLR7-1A with the CAR T cell therapy not only repolarizes TAMs and MDSCs from an M2-like anti-inflammatory to M1-like pro-inflammatory phenotype, but also enhances both CAR T cell and endogenous T cell accumulation in solid tumors while concurrently increasing their states of activation. Because analogous myeloid cells in healthy tissues ar not altered by administration of FA-TLR7-1A, no systemic activation of the immune system nor accompanying weight loss is observed. These data argue that immunosuppressive myeloid cells contribute prominently to the failure of CAR T cells to eradicate solid tumors and suggest that methods to reprogram tumor associated myeloid cells to a more inflammatory phenotype could significantly augment the potencies of CAR T cell therapies.

Indexed as

Myeloid-Derived Suppressor CellsNeoplasmsAnimalsImmunotherapy, AdoptiveMiceMyeloid CellsToll-Like Receptor 7Tumor MicroenvironmentToll-Like Receptor 7CAR T cellscombinational immunotherapymyeloid-derived suppressor cell (MDSC)reprograming tumor microenvironmentTLR7 agonisttumor associated macrophage (TAM)tumor microenvironment (TME)

Identifiers

PMID35250995
PMCPMC8889096
OpenAlexW4213170493

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

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.