The Immunotherapy Revolution

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INTRATUMORAL IMMUNOTHERAPY AND CRYOABLATION FOR CANCER – WELCOME TO Cabo San Lucas, Mexico.

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DOES ACETAMINOPHEN DECREASE THE IMMUNE RESPONSE?

Acetaminophen is one of the foremost frontline medications in relieving pain and discomfort. It’s relatively safe. It’s the most common and cheapest on the market. Of course, anything in excess can be harmful. A few pills too many or combined with alcohol, and it can cause severe liver failure or death. But is that the only risk it poses? It seems not for Immunotherapy patients.

An increased mortality rate of Immunotherapy patients taking Acetaminophen has led to several researchers conducting studies.
These studies have shown that the hazard (H) to progression-free survival rate (PFS) increases when introducing Acetaminophen. Influenced by Acetaminophen, the immune system upregulates Interleukin-10, an immune-suppressive cytokine that decreases inflammation. It also reduces cell death protein 1 (PD-1), which is involved in the immune system’s T-cell response. This makes it harder for the immune system to detect tumor cells.

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Breast Cancer Awareness: Questions & Answers

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Did you know that you can reduce the risk of pancreatic cancer and improve immunotherapy response by doing aerobic exercise?

Thirty minutes of exercise a day can reduce the risk of pancreatic cancer by as much as 50%. Aerobic exercise produces adrenaline (the fight-or-flight hormone). Adrenaline can boost the immune response by enhancing how the body handles signal proteins like Interleukin-15, which activates and increases the proliferation and survival of T-cells, B-cells, and NK (natural killer) cells. For this reason, adrenaline acts as one of the keys to unlocking a broader immune response to pancreatic cancer. Aerobic exercise also releases endorphins that reduce anxiety and depression.

It should be noted that generally, after a surgical procedure, it is recommended to start physical activity gradually under the advice of your health provider.

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DOSTARLIMAB AND THE AMAZING IMMUNOTHERAPY RESULTS IN RECTAL CANCER

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Complete response in 12 Out of 12 Patients with Rectal Carcinoma using Immunotherapy

On June 5, published by Cercek et al. in The New England Journal of Medicine, a small trial of 12 patients with stage 2-3 rectal cancer was treated with the PD-1 inhibitor, dostarlimab.   Amazingly, they reported that 12 out of 12 had a complete response. Clearly very exciting and goes with my feeling that most cancer patients need to be allowed to be treated with Immunotherapy, especially if other treatments have failed. There is one special consideration in the study; the patients had what is known as a mismatch repair deficient tumor. What is mismatch repair? It is the ability to fix incorrectly inserted bases of DNA that occur during the copying of the DNA. If this process does not function correctly, more DNA errors will accumulate. The more errors, the more different the cancer DNA will be from normal cells. This gives the immune system more targets, making cancer more receptive to Immunotherapy. Unfortunately, like many other cancers, mismatch deficiency is in the minority of colorectal cancer, 15% or less. Certainly, it is essential to identify patients with mismatch deficiency and consider Immunotherapy. That is undoubtedly a common practice in evaluating the biopsy of a tumor. There are also other aspects beyond mismatch repair, such as tumor mutational burden and other mutations associated with DNA repair. Also, in some cases, certain medications can be used to block DNA repair, potentially increasing the potential to respond to Immunotherapy.

There are a few questions that arise from this trial. One question is whether dostarlimab is superior to Opdivo or Keytruda, even though all are in the same class of drugs as PD-1 inhibitors. The results seemed similar in prior trials where dostarlimab and Keytruda were used. We may see more head-to-head trials to answer this question in the future. The next question is what can be done to make the majority of patients who don’t have mismatch deficiency respond as well. Though there are many complex aspects of the immune response, one key one is to increase the immune cell infiltration into cancer. One technique is injecting immune agents into the tumor that calls the immune cells to the tumor. This now alerts the immune cells to cancer and can increase the ability to respond to other Immunotherapy. This is a way to equalize the playing field for patients who don’t have mismatch repair to be more like those who do.

Certainly, this study further demonstrates to the public what we in the scientific community already knew, that it is possible to have incredible responses with Immunotherapy. And we know the playbook and can expand this out to the majority of other cancers. That is precisely what we are doing with our patients, bringing the treatments of the future to them today.

By Dr. Jason Williams

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