How Does Cancer Manipulate The Immune System?

Cancer immunotherapy drugs, responsible for implementing the body’s immune system to combat tumors, have continued to show promise yet these drugs have still failed many cancer patients. A new study could show how some stubborn cancers continue to dodge therapies, and perhaps offer some insight towards getting a way out.

Cancer Cells

Cancer Cells

Published on Thursday April 4th 2019 in the journal Cell, the study zeros in on prostate and colorectal cancer. These two types of cancers are among top that seem highly resistant to immunotherapy drugs.

Research and findings

The drugs work by blocking signals sent by the tumors to confuse and puzzle the immune system. The signals are usually sent through a specific molecule (PD-L1) that is located on the surface of specific cells. The problem is PD-L1, will not necessarily appear on all tumors, it therefore makes it hard for the immunotherapy drugs to interfere with the signal sent by the cancer in such cases.

This new study is just but a part of a developing research that implies that even though tumors may lack PD-L1 on the surface, it is the same mechanism used to manipulate the immune system. The molecule, instead of showing on the tumor’s surface, it directly goes into the body. It then travels in to the lymph nodes, and tricks the cells that reside there.

According to Dr. Robert Blelloch- a senior author of the new paper and an associate chairman of the dept. of urology, California University- PD-L1 molecules remotely prevent activation of immune cells.

According to a research by U.C.F.S scientists, they found out that a mouse with prostate cancer could be cured if the molecule going to the lymph nodes was removed, to stop it from tricking the immune system. After the molecule was removed, the immune system was able to effectively attack the cancer.

It was further discovered that the same mouse’s immune system was able to fight tumors even after the drifting PD-L1 was reintroduced. Based on these findings, Dr. Blelloch said that there is a possibility that the immune system can be trained to recognize a tumor just the same way vaccines train it to recognize a virus.

This research was conducted in laboratory on mice only and yet to be tried on human beings. The Genentech VP of cancer immunology, Dr. Ira Mellman, termed these findings as “most interesting result.”

Dr Mellman said, “As with all mouse experiments, it is easier to get insights into mechanisms, unfortunately its translation in human is still unclear,” He remains quite skeptical, but he plans to have a meeting with Dr. Blelloch real soon and discuss the implications of this study.

New research and work published in 2018 in the journal Nature showed that skin cancer tumors produced PD-L1 molecules that significantly suppressed the immune system.

Exosomal- when PD-L1 molecule bits travel outside the tumor cell. Discovery of the role of exosomal in streamlining a vital area in the medical field has been a promising milestone. In 2018, two scientists -Tasuku Honjo of Kyoto University in Japan and James Allison of Houston’s M.D. Anderson Cancer Center- won the Nobel Prize for doing remarkable work in immunotherapy.

More extensive, research and studies are underway and are aimed at not only refining the therapies but also at looking for additional molecules which may be involved in the feeble relationship between the immune system and cancer.

Although far more studies are necessary, Dr. Blelloch is already thinking of finding ways to actualize the findings discovered into concrete therapy that can be exploited for prostate and colorectal cancer.

Conclusion

If the research finding were to be formulated into a safe therapy then it would be a new dawn and great news for cancer patients. However, messing with PD-L1 heading to lymph node may have severe long term implications like anti-tumor immunity

References
  • PDL1 (Immunotherapy) Tests
  • Henegan, John C., and Guru Sonpavde. “Promising Immunotherapy for Prostate Cancer.” Expert Opinion on Biological Therapy, vol. 18, no. 2, 2018, pp. 109–120.
  • Bilušić, Marijo, et al. “Immunotherapy of Prostate Cancer: Facts and Hopes.” Clinical Cancer Research, vol. 23, no. 22, 2017, pp. 6764–6770.

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