Moffitt Researchers Discover Mechanism that Regulates Anti-Tumor Activity of Immune Cells in Ovarian Cancer | MoffittYet another conundrum to ponder for intelligent [sic] design creationists who like to believe their putative designer is one and the same as the allegedly all-loving god of the Christian Bible.
Why has it given some women a better immune system for dealing with ovarian cancers than it gave to others?
This difference was the subject of an investigation by researchers from the Moffitt Cancer Center to discover what it was that meant the outcomes from immunotherapies for this cancer were so variable from one woman to another. What they discovered was:
Immunotherapeutic drugs activate T cells, a type of immune cell, to put up a defense against tumor cells. Immunotherapies are approved to treat several different types of cancer and have greatly changed the standard of care and improved patient outcomes. However, in ovarian cancer, clinical studies using immunotherapies aimed at stimulating T cells resulted in modest response rates. Studies have suggested that cancer patients who have a higher presence of other immune cells, such as plasma and memory B cells, could respond better to immunotherapies, but how these cell types promote better outcomes is unclear. Moffitt researchers wanted to confirm whether antibodies produced by these cells are associated with better outcomes and assess how these cells contribute to the spontaneous anti-tumor immune response against ovarian cancer.These findings were published open access in Nature a couple of days ago:
The researchers analyzed a panel of 534 samples from ovarian cancer patients and found that patients who had a higher infiltration of B cells or B cell-derived plasma cells had better outcomes. B cells are a type of immune cell that produce antibodies and express one of five types of B cell receptors on their surface: IgM, IgD, IgG, IgE or IgA. These isotypes regulate different B cell signaling pathways and control B cell processes.
The surprise came when, upon further analysis of the samples, the Moffitt team discovered that the antibodies produced by B and plasma cells were predominantly of the IgA subtype, followed by IgG.
“We found that the presence of IgA regulated downstream signaling pathways of the ovarian cancer cells. Specifically, IgA resulted in inhibition of the RAS signaling pathway, which is known to contribute to ovarian cancer development,” said Jose Conejo-Garcia, M.D., Ph.D., chair of Moffitt’s Immunology Department.
This inhibition of RAS sensitized the tumor cells to T cell mediated cell killing, produced by both novel CAR T cells and tumor-infiltrating lymphocytes. The team also assessed that IgA and IgG secreted by the B cells recognized specific ovarian tumor cell surface markers and stimulated other immune cells called myeloid cells to target ovarian cancer cells for destruction.
[...]
The findings indicate that immunotherapies that boost both coordinated B and T cell responses against ovarian cancer, an immunogenic disease currently resistant to checkpoint inhibitors, are likely to show superior therapeutic benefit,” said Subir Biswas, Ph.D., first author and postdoctoral fellow in the Conejo-Garcia lab.
The question then for intelligent [sic] design advocates, appart from the obvious one about why this putative designer was malevolent enough to create cancers in the first place, is why, if it gave some women the ability to defend themselves from ovarian cancers, it didn't give them all this ability?Abstract
Most ovarian cancers are infiltrated by prognostically relevant activated T cells1,2,3, yet exhibit low response rates to immune checkpoint inhibitors4. Memory B cell and plasma cell infiltrates have previously been associated with better outcomes in ovarian cancer5,6, but the nature and functional relevance of these responses are controversial. Here, using 3 independent cohorts that in total comprise 534 patients with high-grade serous ovarian cancer, we show that robust, protective humoral responses are dominated by the production of polyclonal IgA, which binds to polymeric IgA receptors that are universally expressed on ovarian cancer cells. Notably, tumour B-cell-derived IgA redirects myeloid cells against extracellular oncogenic drivers, which causes tumour cell death. In addition, IgA transcytosis through malignant epithelial cells elicits transcriptional changes that antagonize the RAS pathway and sensitize tumour cells to cytolytic killing by T cells, which also contributes to hindering malignant progression. Thus, tumour-antigen-specific and -antigen-independent IgA responses antagonize the growth of ovarian cancer by governing coordinated tumour cell, T cell and B cell responses. These findings provide a platform for identifying targets that are spontaneously recognized by intratumoural B-cell-derived antibodies, and suggest that immunotherapies that augment B cell responses may be more effective than approaches that focus on T cells, particularly for malignancies that are resistant to checkpoint inhibitors.
Biswas, Subir; Mandal, Gunjan; Payne, Kyle K.; Anadon, Carmen M.; Gatenbee, Chandler D.; Chaurio, Ricardo A.; Costich, Tara Lee; Moran, Carlos; Harro, Carly M.; Rigolizzo, Kristen E.; Mine, Jessica A.; Trillo-Tinoco, Jimena; Sasamoto, Naoko; Terry, Kathryn L.; Marchion, Douglas; Buras, Andrea; Wenham, Robert M.; Yu, Xiaoqing; Townsend, Mary K.; Tworoger, Shelley S.; Rodriguez, Paulo C.; Anderson, Alexander R.; Conejo-Garcia, Jose R.
IgA transcytosis and antigen recognition govern ovarian cancer immunity
Nature (2021). doi: 10.1038/s41586-020-03144-0
Copyright: © 2021 The authors. Published by Springer Nature Limited
Open access
Reprinted under a Creative Commons Attribution 4.0 International License (CC BY 4.0)
What we have here, if you believe in this magic intelligent [sic] designer, is yet another example of where this supposed designer has designed a perfectly good system, then elected to not give it to all its creation, as though it either favours some over others of has a special hatred for some. I give a number of these examples in pages 133-150, in my book, The Malevolent Designer: Why Nature's God is not Good
- Elephants Don’t Get Cancer.
- Bats’ Superior Immune System.
- Bird’s Superior Eyes.
- Birds’ Superior Respiratory System.
- Sharks’ Superior Immune System.
- Amphibians’ Superior Regenerative Abilities.
No comments :
Post a Comment
Obscene, threatening or obnoxious messages, preaching, abuse and spam will be removed, as will anything by known Internet trolls and stalkers, by known sock-puppet accounts and anything not connected with the post,
A claim made without evidence can be dismissed without evidence. Remember: your opinion is not an established fact unless corroborated.