Cancer cells like to hide from the immune system. But to do this, they must turn immune cells into personal disguises. Certain drugs turn down one of the disguises since naked cancer cells cannot hide from the immune system. And recent research suggests that a cannabis ingredient known as CBG can synergize with one of these anti-cancer drugs. (1)
Mutated cells regularly form throughout the body. Essentially, cells with the same broken code multiply thousands of times over and eventually produce cancerous tissue. To counter this effect, though, antigens scan the body and tag parts they don’t recognize as ‘self’. The immune system then sends macrophages and other eat-me-signals to consume tagged cells, which should include cancerous tissues. Therefore, to avoid the vicious immune system, cancer must hide.
A protein known as Programmed Death Factor 1 (PD-1) is one of four known disguises that hide damaged or intrusive cells. Strong intruders and freshly broken cells avoid immune surveillance with a PD-1 cloaking device, possibly multiplying into a cancerous growth. PD-1 blockers are a type of drug, usually delivered as a monoclonal antibody, prescribed to cancer patients whose T cells express large quantities of PD-1 markers. Unfortunately, though, PD-1 blockers are often insufficient since cancer is complex and has several backup defenses.
Cannabinoids in the tumor microenvironment
Recent studies suggest that THC, an intoxicating cannabinoid found in cannabis, does not negatively affect cancer-defending PD-1 blockers. (2) But we did not have the same answers for minor cannabinoids. New experiments on mice and human cancer cell lines offer preliminary results with a promising outcome for cannabigerol (CBG).
Published in Oncoimmunology by Taylor and Francis and authored by researchers from Technion-Israel Institute of Technology and the Hebrew University of Jerusalem, a new study looks at cannabis extracts in the tumor microenvironment. They separated the extract into various parts to identify the effective ingredient. And out of cannabis’s spectrum, cannabigerol (CBG) reduced tumor mass more prominently than CBN or other major cannabinoids.
Important immune cells, known as macrophages, exist in two polar-opposite states. Depolarized (M1) macrophages engulf tagged cells, commanding killer T cells to destroy the intruder. Whereas polarized (M2) macrophages counterintuitively silence the immune system, disguising cancerous cells. And immunosuppression impairs PD-1 blockers and other don’t-eat-me-signals.
Tumors learn to polarize macrophages, keeping themselves hidden. Cells that have become cancerous release special cytokines that swap deadly white blood cells into their M2 state. It turns out that CBG inhibits that particular cytokine, a colony-stimulating factor (CSF-1), which helps keep macrophages depolarized in their killer M1 position. CBG ultimately liberates killer T cells, which can increase the effectiveness of PD-1 blockers and other anti-cancer drugs.
Tumors after cannabinoids and anti-cancer drugs
Researchers injected mice with skin cancer cells. They later dosed them with an anti-PD-1 antibody combined with CBG and compared the results with either treatment alone next to tumor-bearing mice given no treatment. CBG and anti-PD-1 drugs significantly reduced tumor volume by 60 to 70 percent in mice after fourteen days.
The result occurred with a CBG:CBN dominant fraction of cannabis extract. Negative results from synthetic CBN compared to synthetic CBG further confirmed results from cannabis extracts. Whereas THC, CBD, and synthetic CBN minimally reduced tumor volume. And while research conducted in mice and on human cancer cell lines fails to provide immediate answers for patients. In conclusion, results indicating exactly how CBG can synergize with anti-cancer drugs further demand precisely formulated cannabinoid medicines.
Stay connected with Uprooted Concepts next week to read how CBG integrated into a success story for one cancer patient.
Sources
Wyrobnik I, Steinberg M, Gelfand A, et al. Decreased melanoma CSF-1 secretion by Cannabigerol treatment reprograms regulatory myeloid cells and reduces tumor progression. Oncoimmunology. 2023;12(1):2219164. Published 2023 Jun 11. doi:10.1080/2162402X.2023.2219164
Waissengrin B, Leshem Y, Taya M, et al. The use of medical cannabis concomitantly with immune checkpoint inhibitors in non-small cell lung cancer: A sigh of relief?. Eur J Cancer. 2023;180:52-61. doi:10.1016/j.ejca.2022.11.022