James P. Crowley, Professor of Medicine Emeritus at Brown University, shared Miguel Bronchud’s, Co-Founder at Regenerative Medicine Solutions, post on LinkedIn, adding:
“‘Dendritic cells (DCs) present antigens from apoptotic cancer cells (or directly injected mRNA vaccines) to T cells, enabling T cell activation and infiltration into tumors.
Although great advances have been made to enhance the function of T cells in the cancer-immunity cycle, strategies for effective therapeutic targeting of tumor-infiltrating DCs remain to be developed.
In many ways, dendritic cells can act as both ‘players and referees‘ of the immediate immune response?
Of particular interest are cDC1s (type | conventional DCs), a DC subpopulation with the distinctive ability to crosspresent antigens from apoptotic tumor cells to CD and T cells that serve as cytotoxic effector cells in tumor immunity.
But in some cases (at least in mice), cDC2 type cells are equally effective (often in a redundant sort of way, but their more selective roles are still being evaluated, especially in the context of mRNA vaccines like for COVID19)’
DCs can shift trom tolerogenic to highly immune stimulatory states in response to signals from cytokines and pattern-recognition receptors.”
Quoting Miguel Bronchud’s post:
“Dendritic cells- antigen presenting cells or ‘architects‘ of different immune responses landscapes? Or both?
Protective cancer immunity requires cooperative action by two major immune cell populations: dendritic cells (DCs) and T cells.
DCs present antigens from apoptotic cancer cells ( or directly injected mRNA vaccines) to T cells, enabling T cell activation and infiltration into tumors. Although great advances have been made to enhance the function of T cells in the cancer-immunity cycle, strategies for effective therapeutic targeting of tumor-infiltrating DCs remain to be developed.
In many ways, dendritic cells can act as both ‘players and referees‘ of the immediate immune response?
Of particular interest are cDC1s (type I conventional DCs), a DC subpopulation with the distinctive ability to ‘crosspresent’ antigens from apoptotic tumor cells to CD8 T cells that serve as cytotoxic effector cells in tumor immunity. But in some cases (at least in mice), cDC2 type cells are equally effective (often in a redundant sort of way, but their more selective roles are still being evaluated, especially in the context of mRNA vaccines like for COVID19)…
RATIONALE: DCs can shift from tolerogenic to highly immune stimulatory states in response to signals from cytokines and pattern-recognition receptors.
X. Zhang et al., Science 393, eaea1200 (2026) Investigated the role of the CARM1 (coactivator-associated arginine methyltransferase 1) epigenetic enzyme in cDC1s, which acts as a transcriptional co-activator for several transcription factors by methylating arginine resides of chromatin-associated proteins.
CARM1 was previously shown to play a cancer cell–intrinsic role by acting as a transcriptional co-activator of oncogenic transcription factors, including c-Myc.
X. Zhang et al., Science 393, eaea1200 (2026) discovered that inactivation of the Carm1 gene in cDC1 enhanced their ability to cross-present antigens from apoptotic cancer cells to CD8 T cells, resulting in enhanced T cell activation and proliferation.
Targeting of the CARM1 epigenetic enzyme enhances dendritic cell function in the cancer-immunity cycle.
See figure:
Title: The CARM1 epigenetic enzyme inhibits cross-presenting dendritic cell function in cancer immunity
Authors: Xixi Zhang, Sherin Xirenayi, Ye Zhao, Wen Wang, Yuyang Han, Miguel Sobral, Shawn Kang, Chi Zhang, Graham L. Barlow, Jason Pyrdol, Jae-Won Cho, Kun Huang, Xiaohan Ning, Martin Hemberg, Guo-Cheng Yuan, Eliezer M. Van Allen, David J. Mooney, Kai W. Wucherpfennig
A) cDC1 function is impaired in tumors because of TGFβ-induced up-regulation of the CARM1 epigenetic enzyme.
B) CARM1 inhibition in cDC1s increases cDC1 infiltration into tumors, migration to tumor-draining lymph nodes, and cross-presentation of tumor antigens to CD8 T cells, resulting in enhanced tumor immunity.
Local delivery of a small-molecule CARM1 inhibitor with a neoantigen-based cancer vaccine enhanced cDC1 recruitment and expansion of neoantigen-specific T cells, resulting in more durable tumor control.
This pathway was also conserved in human cDC1 differentiated from hematopoietic stem cells.”
Other articles about immunotherapy and dendritic cells on OncoDaily.