WHY????? And what should we do when it fails? Dismaying questions with no clear answers, right? But, researchers are working on them!
First - what to do when immunotherapy fails?
What to Do When Anti-PD-1 Therapy Fails in Patients With Melanoma. Mooradian, Sullivan. Oncology, April 2019.
You should be able to get the entire article via this link:
Note: We already know that combining ipi with anti-PD-1 provides improved response rates as compared to anti-PD-1 as monotherapy, though for some, even that is not enough. Here is a primer of basic melanoma treatments I put together that covers some of the treatments described above:
Melanoma Intel: A primer for current standard of care and treatment options
But, back to the first question ~ as Fierce Biotech put it in their article linked here: What causes immuno-oncology drug resistance? 2 research teams uncover clues!
The article notes:
SO...two very different things are addressed within this article....
1. The cooties in our gut make a difference. I've been writing about this for some time. Here is a recent report with links to many more within: DECREASED progression free survival in melanoma patients treated with antibiotics prior to or at start of immunotherapy!!!! Side note: Additional studies show that you have to consume the real deal. Probiotics out of a bottle won't do the trick. In fact, attaining your cooties that way may actually DECREASE your response to immunotherapy.
2. The whole PD-L1 positive vs NOT positive thing! We have long known that having PD-L1 positive tumors does not guarantee a response. AND... folks with tumors NEGATIVE for PD-L1 can still sometimes gain one! Here are a bunch of reports addressing the PD-L1 conundrum!
There is also this report on the same research in the NY Times from April: Cancer’s Trick for Dodging the Immune System, where the author notes: