This is a very good Feb 2023 article but it’s best to scroll down to get out of the weeds to the crux of the biscuit.
The crux of this biscuit is a well known inflammatory cytokine CCL20 and it’s receptor CCR6.
nature.com/articles/s41467-...
Dissecting the immune suppressive human prostate tumor microenvironment via integrated single-cell and spatial transcriptomic analyses
We hypothesized that, there is a correlation between the immunosuppressive myeloid and T-cell phenotype in our dataset as our group previously showed that immunosuppressive myeloid cells contributed to the exhausted T-cell phenotype in the setting of metastatic prostate cancer89. Indeed, we observed in our dataset a correlation between MDSC and Treg activity signatures in TIMo and Tregs, respectively; pointing to the role of myeloid cells in establishing a T-cell suppressive and pro-tumor microenvironment. Through computational heuristics, we identified CCL20-CCR6 as a potential ligand-receptor axis that may allow for communication between TIMo and Tregs, respectively. We showed that blocking one such signaling axis using CCL20-blocking antibody significantly reduced tumor growth in a subcutaneous model of syngeneic PCa. This axis is implicated in several inflammatory and immune-activated states, including autoimmune disease90. The potential for modulating the axis to reduce the activated states of immune cells has been extensively explored and led to early-stage clinical trials91,92.
references #90
Modulation of the CCR6-CCL20 Axis: A Potential Therapeutic Target in Inflammation and Cancer
2. Inhibitors of CCR6–CCL20
CCR6–CCL20 axis inhibitors include (i) antibodies that bind CCL20; (ii) antibodies that bind CCR6; (iii) small molecule inhibitors of CCL20; (iv) small molecule inhibitors of CCR6; (v) small interfering RNA (siRNA) that hybridizes to a nucleic acid encoding CCL20 and (vi) siRNA that hybridizes to a nucleic acid encoding CCR6 [17]. Most of the studies undertaken up until now depended heavily on the utilization of neutralizing monoclonal or polyclonal antibodies.
“Current prescription medicines consist of disease-modifying drugs which ameliorate symptoms and pathology through non-specific suppression of inflammatory pathways. The blockade of inflammatory cytokines and products that up-regulate pro-inflammatory chemokines is known to further induce inflammation. The biological agents Infliximab, Tocilizumab, and Etanercept, have been used to block CCL20, which is otherwise known to markedly increase inflammation in autoimmune and inflammatory disorders. Infliximab is an anti-tumor necrosis factor-alpha (TNF-α) monoclonal antibody that is used to neutralize the inflammatory cytokine TNF-α; Etanercept has an anti-TNF-α modified as a fusion protein; and Tocilizumab is an antibody produced against interleukin-6 receptor (IL-6R). All three of these agents have demonstrated a significantly reduced CCL20 concentration below serum baseline values, and they are combined as supplements as a routine pharmacotherapy. Infliximab depresses TNF-induced CCL20 upregulation via the nuclear factor kappa B (NF-kB) pathway in synoviocytes which causes rheumatoid arthritis. Blockade of IL-6 modulates the CCR6–CCL20 axis by preventing the differentiation of TH17 cells from CD4+ T cell populations [18].
Early studies on the specific blocking of either CCR6 or CCL20 included the transfer of CD4+ T cells from Sakaguchi mice into severe combined immunodeficiency (SCID) mice and the administration of a monoclonal antibody (mAb) against CCR6 in a rheumatoid arthritis model. The mAb administered mice exhibited lowered migration of TH17 cells to the joints with a recognizably reduced disease severity. Other research has mostly pivoted around CCR6−/− mice, pointing in the direction of a disrupted CCR6–CCL20 axis which affects immune cell chemotaxis and a discernible change in immune homeostasis. In the guts of inflammatory bowel disease (IBD) models, CCR6 deficiency indicated pronounced changes in the overall histology at the Peyer’s patches [18].“
Another 2023 article on CCR6 and CCL20
CCR6 as a Potential Target for Therapeutic Antibodies for the Treatment of Inflammatory Diseases
Abstract
The CC chemokine receptor 6 (CCR6) is a G protein-coupled receptor (GPCR) involved in a wide range of biological processes. When CCR6 binds to its sole ligand CCL20, a signaling network is produced. This pathway is implicated in mechanisms related to many diseases, such as cancer, psoriasis, multiple sclerosis, HIV infection or rheumatoid arthritis. The CCR6/CCL20 axis plays a fundamental role in immune homeostasis and activation. Th17 cells express the CCR6 receptor and inflammatory cytokines, including IL-17, IL-21 and IL-22, which are involved in the spread of inflammatory response. The CCL20/CCR6 mechanism plays a crucial role in the recruitment of these pro-inflammatory cells to local tissues. To date, there are no drugs against CCR6 approved, and the development of small molecules against CCR6 is complicated due to the difficulty in screenings. This review highlights the potential as a therapeutic target of the CCR6 receptor in numerous diseases and the importance of the development of antibodies against CCR6 that could be a promising alternative to small molecules in the treatment of CCR6/CCL20 axis-related pathologies.
I find this interesting on using arthritis drugs injected into tumor during immunotherapy instead of steroids.
williamscancerinstitute.com...
The immune system produces proteins, known as chemokines, which are signals that can affect immune function. There is a chemokine named C-C motif ligand 20, also known as CCL20. It is known as an inflammatory protein, often associated with rheumatoid arthritis. However, new evidence links this cytokine with numerous cancers. It seems that CCL20 promotes cancer metastasis. In addition, it increases cancer stem cells and causes T cell exhaustion. These actions will suppress an immune response. There are studies in many cancer types indicating that blocking CCL20 is anti-cancer and may enhance the success of immunotherapy. Surprisingly enough, drugs that can block CCL20 may also reduce autoimmune side-effects from standard PD-1 immunotherapy, such as Opdivo and Keytruda. Unfortunately, patients with autoimmune side effects are typically given steroids to treat these issues, which can reduce the success of immunotherapy.
It seems these arthritis medications would be a better choice because they reduce side effects and increase immunotherapy success. They appear on their own to be cancer immunotherapy.
“So what drugs arthritis am I discussing? I am talking about three FDA-approved medications, Infliximab, Tocilizumab, and Etanercept. These drugs all indirectly block CCL20. “
Infliximab, Tocilizumab, and Etanercept all require injection or infusion and prescription with serious side effects that need to be monitored closely. So that excludes them from my list of available medicines.
Aside from the article above I myself already have a DMSO extract from budding spring leaves of Juglans nigra (black walnut) which is a good source of gallotannins.
I will start using that again with egcg orally.
