How A Checkpoint Inhibitor Works to Fight Metastatic Melanoma


Erin Azuse

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Your immune system has an important job. Not only must it attack harmful cells to protect you from getting sick, it must also recognize your body’s own cells so it leaves them alone. In some cases, however, cancer cells can trick the immune system, so they escape the attack and continue to grow.

A newer method of cancer treatment called immunotherapy hopes to change that. Researchers are learning how to help the immune system fight against cancer cells. For patients with metastatic melanoma, a cancer that usually starts on the skin and spreads to other locations of the body, a type of immunotherapy known as a checkpoint inhibitor has demonstrated some exciting results.

Leta talks about her journey with advanced melanoma, from discovery to diagnosis to treatment with immunotherapy.

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T cells contain the on/off switch for your immune response.

T cells, or T lymphocytes, are a type of white blood cell and an important part of your immune system. As they circulate throughout your body, they help differentiate between normal and abnormal cells. When the T cell comes across an abnormal cell, it “turns on” the immune response and attempts to destroy it.  Conversely, when the T cell comes across a healthy cell, the immune response is suppressed or “turned off”.  This is known as a “checkpoint” and is how your body protects itself from harming its own cells and tissues.  

Yet some cancer cells are able to evade destruction by hacking these same checkpoints to inactivate the T-cell. They disguise themselves so that the T cell sees them as normal cells. This turns off or lessens the immune system’s response to the cancer cells, allowing them to thrive.  

Checkpoint inhibitors help keep the T cells from turning off.

Checkpoint inhibitors, a class of medications used to treat cancer, do just what their name implies. They block the cancer cells from using the checkpoint to turn off the T cells. This allows the T cells to see the cancer cells for what they truly are and helps the immune system mount a full attack. 

Right now, two types of checkpoint inhibitors are used to fight metastatic melanoma, PD-1 inhibitors and CTLA-4 inhibitors. Each class refers to the specific checkpoint protein that the medication targets. Researchers are currently studying other checkpoints and trying to develop new checkpoint inhibitors to boost the body’s immune response to cancer.

They do so with good reason. Historically, metastatic melanoma has had a very poor prognosis. Yet with the development of checkpoint inhibitors, studies have shown improvements in overall survival rate and tumor regression for many individuals.

Effects of treatment are usually not immediate.

It is not uncommon for it to take 6 to 12 weeks or longer for the checkpoint inhibitors to begin to work.  Additionally, some patients may even see an increase in tumor size early on in treatment. This may be due to the larger number of activated T cells and immune cells that are present. After some time, however, the tumor may begin to shrink or even disappear.

The immune system boost can sometimes be too big.

In some cases, the use of checkpoint inhibitors can cause the body to attack its own tissues as well, known as an autoimmune response. Patients should be monitored carefully and instructed to contact their doctor if any side effects develop. Usually this can be reversed with a round of steroids or a temporary break in treatment, but for some patients it can lead to serious complications.

There is not one right way to treat metastatic melanoma, or any form of cancer for that matter, since individual responses to different forms of treatment will vary. Yet it is exciting to see new therapies provide patients live longer and enjoy a higher quality of life. Don’t hesitate to talk to your doctor if you would like to learn more about checkpoint inhibitors and other emerging treatments for melanoma.

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Medical Reviewers: William C. Lloyd III, MD, FACS Last Review Date: Dec 23, 2016

© 2016 Healthgrades Operating Company, Inc. All rights reserved. May not be reproduced or reprinted without permission from Healthgrades Operating Company, Inc. Use of this information is governed by the Healthgrades User Agreement.

View Sources

Medical References

  1. Cancer Immunotherapy- Melanoma. Cancer Research Institute.
  2. Immune Checkpoint Inhibitors. Jama Oncology.
  3. Immune Checkpoint Inhibitors to Treat Cancer. American Cancer Society.
  4. Immunotherapy: Using the Immune System to Treat Cancer. NIH National Cancer Institute.

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