New avenues for the optimzation of dendritic cell-based cancer
immunotherapies

Date:
October 12, 2021
Source:
University of Helsinki
Summary:
A recent study reveals that inhibiting certain adhesion receptors
on the surface of dendritic cells, the main antigen-presenting
cells of the immune system, enhances antitumor responses.



FULL STORY ==========================================================================
A recent study from the University of Helsinki reveals that inhibiting
certain adhesion receptors on the surface of dendritic cells, the main
antigen- presenting cells of the immune system, enhances antitumour
responses.


========================================================================== Dendritic cells are the main antigen-presenting cells of the immune
system and are essential for "kicking off" the immune response against infectious agents and tumours. Beta2-integrins are adhesion receptors
found on the surface of these cells, which mediate the interactions
between the cell and its environment.

"We have found that these integrin-mediated interactions dampen
the functionality of dendritic cells and their migration. This
happens by regulating the gene expression programme of the cell. In
particular, integrins regulate epigenetic changes such as the chemical modifications of histones, the proteins that DNA is wrapped around to
make chromatin. This affects how tightly DNA is wound around the histones
and how 'open' the chromatin is -- which in turn determines whether a
specific gene expression can occur," explains Susanna Fagerholm, from
the University of Helsinki.

Importantly, the researchers found that when integrins are switched off, dendritic cells switch on a gene expression programme that makes them
better at mediating T cell activation and tumour rejection. Increased
tumour rejection can also be induced artificially by manipulating these pathways in normal dendritic cells.

This study reveals that beta2-integrins function as negative regulators
of dendritic cell programming. By inhibiting these receptors, dendritic
cells' anti-tumour responses become more effective. "This works a bit
like check-point inhibition, which targets T cells, but here the target
is the dendritic cells.

When we "release the breaks" of the dendritic cells, it makes them better
at activating T cells. This opens up new possibilities for improving
dendritic cell-based cancer immunotherapies already in use in the clinic," Fagerholm concludes.

========================================================================== Story Source: Materials provided by University_of_Helsinki. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Carla Guenther, Imrul Faisal, Manlio Fusciello, Maria Sokolova,
Heidi
Harjunpa"a", Mette Ilander, Robert Tallberg, Maria Kristina
Vartiainen, Ronen Alon, Jose-Maria Gonzalez-Granado, Vincenzo
Cerullo, Susanna Carola Fagerholm. b2-Integrin Adhesion Regulates
Dendritic Cell Epigenetic and Transcriptional Landscapes to Restrict
Dendritic Cell Maturation and Tumor Rejection. Cancer Immunology
Research, 2021; DOI: 10.1158/2326- 6066.CIR-21-0094 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/10/211012091855.htm

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