A Connection between CCR5 Cellular Surface Expression in Tumors and in Long Haulers
What is the function of the T-Reg or T-Regulatory Cells or T-Suppressor Cells? The Regulatory Cells are the Suppressor Cells.
These cells prevent the T-Cytotoxic Cells, (Natural Killer Cells), from killing your own cells. T-Cytotoxic, NKC are crazy. They can destroy your pancreas. They can destroy your own Thymus. They can destroy your nose cells, your muscle cells, etc... Who tells these Natural Killer Cells to stay away from your own cells? The T-Regulatory Cells aka T-Suppressor Cells do that. The T-Regs tell the NKCs to stay away from the body's cells and to go after the foreigners.
If you have a problem in the T-Regs, then the T-Lymphocytes, (T-Cytotoxic, Natural Killer Cells), will then attack your own cells in a phenomenon known as the Auto-Immune Disease such as Lupus for example.
From this video: https://www.youtube.com/watch?v=uxkc6Ql1C-U
0:00: The battle against cancer is fought and won in the tumor micro-environment. Here, cancer cells secrete a cytokine, CCL5 or Rantes to attract supporting cells such as Macrophages and T-Regulatory Cells to encourage tumor growth and metastasis.
0:26: In the tumor microenvironment, the Macrophages are known as Tumor Associated Macrophages, (TAMs), TAMs or M-2 Macrophages. An important discovery in Immuno-Oncology is the Identification of the CCR5 receptor on the cell surfaces of M-2 Macrophages, T-Regs and Tumor Cells.
0:52: During malignant transformation, there is an upregulation of the CCR5 receptor, (in excess of normal), which enhances tumor progression.
1:04: (M-2) Macrophages produce VEGF in response to CCL5 Rantes, which promotes angiogenesis, the formation of blood supply, to support tumor growth. These (M-2) Macrophages also promote metastasis, by stimulating Tumor Cell Proliferation, and invasion into the blood stream where they can circulate throughout the body. It is metastasis (beginning as Circulating Tumor Cells as measured in CytoDyn's Breast Cancer Trials), not the primary tumor, which kills 90% of cancer patients.
1:34: T-Regs also play a critical role in this environment. Initially, other T-Cells, such as NKcells (Natural Killer Cells) & CytoToxic T-Cells, attack the Tumor Cells (& destroy them). ... (The Tumor produces an (over) abundance of CCR5 which attracts an (over) abundance of T-Regs which aims to turn - off the immune system's response to fight tumors.
1:58: The T-Regs affect the NKCells and the CytoToxic T Cells to turn off the "Anti-Tumor" response (with the over-abundance of CCR5). T-Regs "suppress" this T-Cell army by hindering their ability to eliminate cancer cells.
2:15: At CytoDyn, we believe the next breakthrough in Immunotherapy, is Leronlimab. A humanized, monoclonal antibody, which targets CCR5 receptor to win back control for the immune system in the tumor microenvironment in MANY types of cancer.
2:33: Leronlimab blocks the CCR5 receptors and the interactions at CCL5 preventing the detrimental effects of CCR5 over-expression, (over abundance). It knocks out the M-2 population, (which are the "affected/converted" macrophages which promotes angiogenesis and tumor proliferative metastasis). (M-2 population is eliminated with Leronlimab.) and converts all the M-2 macrophages to their original (pre-conversion) M-1 anti-tumor macrophages.
3:01: This repolarization of Pro-Tumor M-2 Macrophage into Anti-Tumor M-1 Macrophage fights cancer rather than promoting Tumor growth. Leronlimab also prevents endovascular migration of Tumor cells and blocks Tumor angiogenesis.
At CytoDyn, we believe there are a variety of potential synergistic mechanisms of action for Leronlimab in Traditional (Chemotherapy and Radiation) and Immuno-Oncological (Check Point Inhibitors, CAR-T Cell therapy, PARP inhibitor) treatments .
//
Contrasting / Comparing / Correlating
//
remember this post:
https://www.reddit.com/r/LeronLimab_Times/com...trial_and/
We said that covid-19 fatigued the immune system and thereby down regulated CCR5 expression on T-Cell surface. The immune system aged and therefore fewer CCR5 cytokines were expressed on the cell's surfaces. It was found that in the patients that responded to Leronlimab treatment, the number of CCR5 cytokines returned back to the normal number if they were originally suppressed.
We said that for the given the level of stimulus, (spike protein) present in the individual, the medulla-vagus nerve axis would determine a certain level of cytokine messaging which should be present based on the magnitude, duration and change in current stimulus, (PID or Proportional Integral Derivative) controller. Essentially, one of the feedbacks into the medulla-vagus nerve axis controller is the quantity of CCR5 communication, signaling and messaging.
Quoting Dr. Otto Yang, “But we found just the opposite,” Yang said. “Patients who improved were those who started with low CCR5 on their T cells, suggesting their immune system was less active than normal, and levels of CCR5 actually increased in people who improved. This leads to the new hypothesis that long COVID in some persons is related to the immune system being suppressed and not hyperactive, and that while blocking its activity, the antibody can stabilize CCR5 expression on the cell surface leading to upregulation of other immune receptors or functions.”
We said that with increasing stimulus, (increasing Spike protein quantity, extended stay or quick increase change in quantity), the PID controller would output via the vagus nerve, chemical commands made to the T-Cells upregulate their CCR5 surface expression thereby upregulating cellular, chemical signaling and messaging to kill and eliminate the invader (stimulus, spike protein).
We found that in long haulers, regardless of the chemical output of the PID controller to increase CCR5 surface expression, the count remained low because the cells themselves were fatigued and exhausted. We found that by adding Leronlimab, even the nominal number of CCR5 cytokines that were expressed on the cells surface, even they were blocked by LL which led to a derivative (change) drop in CCR5 signaling which led to a derivative uptick in PID controller chemical output to increase CCR5 cell expression. By repeating this over the course of 8 injections, Leronlimab was successful in increasing quantity of CCR5 surface expression to normal levels.
This suggests a complex role for CCR5 in balancing inflammatory and antiinflammatory effects, for example, through T regulatory cells.
//
here is where it gets interesting:
In cancer, the tumor secretes an overabundance of CCL5 Rantes which pre-dominantly bonds to most if not all of the CCR5 receptors on the Macrophages and TRegs. This over expression of CCL5, bonds to all the CCR5, thereby down regulating the number of "Free" or "Available" CCR5 receptors on the Macrophage and T-Reg Surface. When this quantity of Available or Free CCR5 on the surface of these cells is reduced, the behavior and function of these Macrophages and T-Regs become Pro-Tumor instead of Anti-Tumor.
This mirrors or is somewhat analogous to what happens in long haulers where the quantity of "Available or Free" CCR5 on the surface of these Macrophages is reduced, (not by the over expression of CCL5 Rantes), but simply due to the fatigue and overwork, and even aging of these Macrophages and T-Regs due to the sheer magnitude and duration of the stimulus, (spike protein).
The problem with cancer/tumors is that it is a lethal pathogen which should be attacked ruthlessly, but it fools the Immune system, (the NK cells and the Tregs), to think that it is normal body tissue by reducing the number of Available CCR5 on their cell surfaces, by binding to all of them with the overabundant expression of CCL5 Rantes which actually tricks the Immune Cells to become Pro-Tumor, expressing VEGF, inducing angiogenesis and the invasion of circulating tumor cells, metastasis, into the blood stream.
In long haulers, the problem is also that there is a loss in the normal quantity of CCR5 expressed on the cell surfaces.
In Cancer, the low Free CCR5 Macrophages and Tregs work to support Tumor growth because they are not aware that it is cancer, but rather, they believe they are supporting a part of the body to grow which somehow became de-vascularized.
In longhaulers, the low Free CCR5 Macrophages and Tregs remain inactive because they are first too fatigued to do anything, and the PID output reaches a plateau output. Secondly, although a pathogen, (stimulus, spike protein) continues to exist, the Macrophages are not motivated to kill it for the time being, sort of like exhausted lions panting while their prey escaped their jaws and the impetus to generate more attack from the lion has not increased and more emphasis is placed on rest. Similarly, the cells have not received a greater chemical command from the PID controller to express more CCR5 on their cell surfaces because it has plateaued. But when Leronlimab is given, all of the Free CCR5 and even the bound unfree, unavailable CCR5 become Free for a second while CCL5 Rantes is released in preference for the preferred Leronlimab with higher affinity. This consumes all the CCR5 with Leronlimab effectively informing the PID loop medulla-vagus nerve controller that it needs to send out a chemical command to increase CCR5 expression on the cell surfaces. This increases # of CCR5 surface expression on T cells. On the next injection of Leronlimab, again, all the free and bound CCR5 become all bound with LL thereby chemically informing the controller that more CCR5 is required on the cell surfaces and an output is made to tell these cells to express more CCR5. This is repeated 8 times and the number of CCR5 receptors returns back to normal base line. This allows the Adaptive Immune System to continue to fight the stimulus, (invader, pathogen, spike protein), as it is completely dependent on CCR5 cytokine communication, signaling and messaging to develop antibodies. Although CCR5 quantities have normalized, the Innate Immune System continues to remain blocked because Leronlimab half life is nearly a month.
Leronlimab binds to CCR5 with an even greater affinity that CCL5 Rantes and therefore renders CCL5 Rantes as useless when it tries to communicate/connect with CCR5.
I said that Leronlimab blocks CCR5's capacity to message the Innate Immune System but not its capacity to message the Adaptive Immune System. A new statement that I will make here, but I say it with about 50% confidence conjecture is that when CCL5 Rantes binds to CCR5, CCR5 is rendered useless. It has no capacity to communicate in either the Innate or the Adaptive Immune System. Effectively, CCR5 is rendered non-existent when CCL5 Rantes binds to it. Essentially CCL5 is a signal which reverses the effect of the M-1 Macrophage and Treg cells and has it work for the enemy.
But Leronlimab overcomes this because Leronlimab binds to CCR5 with higher affinity and is a preferred molecule to bind with CCR5 than CCL5 Rantes. Leronlimab even dislodges CCL5 Rantes for itself to fill that piece, like one magnet stronger than another magnet.
Leronlimab acts as the perfect viral entry inhibitor in HIV.
Leronlimab reduces Innate Immune System Inflammation.
Leronlimab normalizes CCR5 surface expression in Immunosuppression
Leronlimab rights the functionality of Adaptive Immune Cells when they have been tricked or fooled into working for the enemy.
Leronlimab reverses and undoes the disabling/modifying/transforming effects on Macrophages and T-Reg cells induced by CCL5 Rantes.
Leronlimab blocks Innate Immune System Messaging.
Leronlimab permits Adaptive Immune System Messaging
CCL5 Rantes blocks Innate Immune System Messaging and makes Macrophages think tumors are "Self".
CCL5 Rantes blocks Adaptive Immune System Messaging effectively disabling T-Cell/B-Cell communication and antibody development.
By lowering the expression of Available or Free CCR5 on the surfaces of Macrophages, Cancer effectively disables the immune system, (rendering the patient immunodeficient/suppressed/compromised) even rendering it pro-antigen or pro-tumor. By the over expression and over abundance of CCL5 Rantes, cancer reduces the number of available CCR5 cytokine receptors comparable to the number of available CCR5 in long haulers. The macrophages in longhaulers were ineffective.
What is the function of the T-Reg or T-Regulatory Cells or T-Suppressor Cells? The Regulatory Cells are the Suppressor Cells.
These cells prevent the T-Cytotoxic Cells, (Natural Killer Cells), from killing your own cells. T-Cytotoxic, NKC are crazy. They can destroy your pancreas. They can destroy your own Thymus. They can destroy your nose cells, your muscle cells, etc... Who tells these Natural Killer Cells to stay away from your own cells? The T-Regulatory Cells aka T-Suppressor Cells do that. The T-Regs tell the NKCs to stay away from the body's cells and to go after the foreigners.
If you have a problem in the T-Regs, then the T-Lymphocytes, (T-Cytotoxic, Natural Killer Cells), will then attack your own cells in a phenomenon known as the Auto-Immune Disease such as Lupus for example.
From this video: https://www.youtube.com/watch?v=uxkc6Ql1C-U
0:00: The battle against cancer is fought and won in the tumor micro-environment. Here, cancer cells secrete a cytokine, CCL5 or Rantes to attract supporting cells such as Macrophages and T-Regulatory Cells to encourage tumor growth and metastasis.
0:26: In the tumor microenvironment, the Macrophages are known as Tumor Associated Macrophages, (TAMs), TAMs or M-2 Macrophages. An important discovery in Immuno-Oncology is the Identification of the CCR5 receptor on the cell surfaces of M-2 Macrophages, T-Regs and Tumor Cells.
0:52: During malignant transformation, there is an upregulation of the CCR5 receptor, (in excess of normal), which enhances tumor progression.
1:04: (M-2) Macrophages produce VEGF in response to CCL5 Rantes, which promotes angiogenesis, the formation of blood supply, to support tumor growth. These (M-2) Macrophages also promote metastasis, by stimulating Tumor Cell Proliferation, and invasion into the blood stream where they can circulate throughout the body. It is metastasis (beginning as Circulating Tumor Cells as measured in CytoDyn's Breast Cancer Trials), not the primary tumor, which kills 90% of cancer patients.
1:34: T-Regs also play a critical role in this environment. Initially, other T-Cells, such as NKcells (Natural Killer Cells) & CytoToxic T-Cells, attack the Tumor Cells (& destroy them). ... (The Tumor produces an (over) abundance of CCR5 which attracts an (over) abundance of T-Regs which aims to turn - off the immune system's response to fight tumors.
1:58: The T-Regs affect the NKCells and the CytoToxic T Cells to turn off the "Anti-Tumor" response (with the over-abundance of CCR5). T-Regs "suppress" this T-Cell army by hindering their ability to eliminate cancer cells.
2:15: At CytoDyn, we believe the next breakthrough in Immunotherapy, is Leronlimab. A humanized, monoclonal antibody, which targets CCR5 receptor to win back control for the immune system in the tumor microenvironment in MANY types of cancer.
2:33: Leronlimab blocks the CCR5 receptors and the interactions at CCL5 preventing the detrimental effects of CCR5 over-expression, (over abundance). It knocks out the M-2 population, (which are the "affected/converted" macrophages which promotes angiogenesis and tumor proliferative metastasis). (M-2 population is eliminated with Leronlimab.) and converts all the M-2 macrophages to their original (pre-conversion) M-1 anti-tumor macrophages.
3:01: This repolarization of Pro-Tumor M-2 Macrophage into Anti-Tumor M-1 Macrophage fights cancer rather than promoting Tumor growth. Leronlimab also prevents endovascular migration of Tumor cells and blocks Tumor angiogenesis.
At CytoDyn, we believe there are a variety of potential synergistic mechanisms of action for Leronlimab in Traditional (Chemotherapy and Radiation) and Immuno-Oncological (Check Point Inhibitors, CAR-T Cell therapy, PARP inhibitor) treatments .
//
Contrasting / Comparing / Correlating
//
remember this post:
https://www.reddit.com/r/LeronLimab_Times/com...trial_and/
We said that covid-19 fatigued the immune system and thereby down regulated CCR5 expression on T-Cell surface. The immune system aged and therefore fewer CCR5 cytokines were expressed on the cell's surfaces. It was found that in the patients that responded to Leronlimab treatment, the number of CCR5 cytokines returned back to the normal number if they were originally suppressed.
We said that for the given the level of stimulus, (spike protein) present in the individual, the medulla-vagus nerve axis would determine a certain level of cytokine messaging which should be present based on the magnitude, duration and change in current stimulus, (PID or Proportional Integral Derivative) controller. Essentially, one of the feedbacks into the medulla-vagus nerve axis controller is the quantity of CCR5 communication, signaling and messaging.
Quoting Dr. Otto Yang, “But we found just the opposite,” Yang said. “Patients who improved were those who started with low CCR5 on their T cells, suggesting their immune system was less active than normal, and levels of CCR5 actually increased in people who improved. This leads to the new hypothesis that long COVID in some persons is related to the immune system being suppressed and not hyperactive, and that while blocking its activity, the antibody can stabilize CCR5 expression on the cell surface leading to upregulation of other immune receptors or functions.”
We said that with increasing stimulus, (increasing Spike protein quantity, extended stay or quick increase change in quantity), the PID controller would output via the vagus nerve, chemical commands made to the T-Cells upregulate their CCR5 surface expression thereby upregulating cellular, chemical signaling and messaging to kill and eliminate the invader (stimulus, spike protein).
We found that in long haulers, regardless of the chemical output of the PID controller to increase CCR5 surface expression, the count remained low because the cells themselves were fatigued and exhausted. We found that by adding Leronlimab, even the nominal number of CCR5 cytokines that were expressed on the cells surface, even they were blocked by LL which led to a derivative (change) drop in CCR5 signaling which led to a derivative uptick in PID controller chemical output to increase CCR5 cell expression. By repeating this over the course of 8 injections, Leronlimab was successful in increasing quantity of CCR5 surface expression to normal levels.
This suggests a complex role for CCR5 in balancing inflammatory and antiinflammatory effects, for example, through T regulatory cells.
//
here is where it gets interesting:
In cancer, the tumor secretes an overabundance of CCL5 Rantes which pre-dominantly bonds to most if not all of the CCR5 receptors on the Macrophages and TRegs. This over expression of CCL5, bonds to all the CCR5, thereby down regulating the number of "Free" or "Available" CCR5 receptors on the Macrophage and T-Reg Surface. When this quantity of Available or Free CCR5 on the surface of these cells is reduced, the behavior and function of these Macrophages and T-Regs become Pro-Tumor instead of Anti-Tumor.
This mirrors or is somewhat analogous to what happens in long haulers where the quantity of "Available or Free" CCR5 on the surface of these Macrophages is reduced, (not by the over expression of CCL5 Rantes), but simply due to the fatigue and overwork, and even aging of these Macrophages and T-Regs due to the sheer magnitude and duration of the stimulus, (spike protein).
The problem with cancer/tumors is that it is a lethal pathogen which should be attacked ruthlessly, but it fools the Immune system, (the NK cells and the Tregs), to think that it is normal body tissue by reducing the number of Available CCR5 on their cell surfaces, by binding to all of them with the overabundant expression of CCL5 Rantes which actually tricks the Immune Cells to become Pro-Tumor, expressing VEGF, inducing angiogenesis and the invasion of circulating tumor cells, metastasis, into the blood stream.
In long haulers, the problem is also that there is a loss in the normal quantity of CCR5 expressed on the cell surfaces.
In Cancer, the low Free CCR5 Macrophages and Tregs work to support Tumor growth because they are not aware that it is cancer, but rather, they believe they are supporting a part of the body to grow which somehow became de-vascularized.
In longhaulers, the low Free CCR5 Macrophages and Tregs remain inactive because they are first too fatigued to do anything, and the PID output reaches a plateau output. Secondly, although a pathogen, (stimulus, spike protein) continues to exist, the Macrophages are not motivated to kill it for the time being, sort of like exhausted lions panting while their prey escaped their jaws and the impetus to generate more attack from the lion has not increased and more emphasis is placed on rest. Similarly, the cells have not received a greater chemical command from the PID controller to express more CCR5 on their cell surfaces because it has plateaued. But when Leronlimab is given, all of the Free CCR5 and even the bound unfree, unavailable CCR5 become Free for a second while CCL5 Rantes is released in preference for the preferred Leronlimab with higher affinity. This consumes all the CCR5 with Leronlimab effectively informing the PID loop medulla-vagus nerve controller that it needs to send out a chemical command to increase CCR5 expression on the cell surfaces. This increases # of CCR5 surface expression on T cells. On the next injection of Leronlimab, again, all the free and bound CCR5 become all bound with LL thereby chemically informing the controller that more CCR5 is required on the cell surfaces and an output is made to tell these cells to express more CCR5. This is repeated 8 times and the number of CCR5 receptors returns back to normal base line. This allows the Adaptive Immune System to continue to fight the stimulus, (invader, pathogen, spike protein), as it is completely dependent on CCR5 cytokine communication, signaling and messaging to develop antibodies. Although CCR5 quantities have normalized, the Innate Immune System continues to remain blocked because Leronlimab half life is nearly a month.
Leronlimab binds to CCR5 with an even greater affinity that CCL5 Rantes and therefore renders CCL5 Rantes as useless when it tries to communicate/connect with CCR5.
I said that Leronlimab blocks CCR5's capacity to message the Innate Immune System but not its capacity to message the Adaptive Immune System. A new statement that I will make here, but I say it with about 50% confidence conjecture is that when CCL5 Rantes binds to CCR5, CCR5 is rendered useless. It has no capacity to communicate in either the Innate or the Adaptive Immune System. Effectively, CCR5 is rendered non-existent when CCL5 Rantes binds to it. Essentially CCL5 is a signal which reverses the effect of the M-1 Macrophage and Treg cells and has it work for the enemy.
But Leronlimab overcomes this because Leronlimab binds to CCR5 with higher affinity and is a preferred molecule to bind with CCR5 than CCL5 Rantes. Leronlimab even dislodges CCL5 Rantes for itself to fill that piece, like one magnet stronger than another magnet.
Leronlimab acts as the perfect viral entry inhibitor in HIV.
Leronlimab reduces Innate Immune System Inflammation.
Leronlimab normalizes CCR5 surface expression in Immunosuppression
Leronlimab rights the functionality of Adaptive Immune Cells when they have been tricked or fooled into working for the enemy.
Leronlimab reverses and undoes the disabling/modifying/transforming effects on Macrophages and T-Reg cells induced by CCL5 Rantes.
Leronlimab blocks Innate Immune System Messaging.
Leronlimab permits Adaptive Immune System Messaging
CCL5 Rantes blocks Innate Immune System Messaging and makes Macrophages think tumors are "Self".
CCL5 Rantes blocks Adaptive Immune System Messaging effectively disabling T-Cell/B-Cell communication and antibody development.
By lowering the expression of Available or Free CCR5 on the surfaces of Macrophages, Cancer effectively disables the immune system, (rendering the patient immunodeficient/suppressed/compromised) even rendering it pro-antigen or pro-tumor. By the over expression and over abundance of CCL5 Rantes, cancer reduces the number of available CCR5 cytokine receptors comparable to the number of available CCR5 in long haulers. The macrophages in longhaulers were ineffective.
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