The Immunotherapy Paradox in Obese Cancer Patients

The Immunotherapy Paradox in Obese Cancer Patients


What we know is that
obesity is becoming a pandemic in Western countries. And it is also highly
associated with cancer incidents and cancer development. In fact, it’s predicted that
obesity will overtake smoking as the number one cause
of preventable cancers. So we were trying to understand
how patient intrinsic factors interact with the immune
system and what that means in terms of immunotherapy. Our previous data had shown
that for immunotherapy, sometimes we can see increased
toxicity in obese patients. And we had seen these with
strong immunostimulatory therapies, like cytokine
therapies and things like that. And so we wanted to
follow up on those studies by looking at the toxicity
of checkpoint inhibitors since they’ve become
so clinically relevant. So our key findings
are that as opposed to the immunostimulatory
therapies that we don’t see
increased toxicity in obese patients treated with
checkpoint inhibitor therapy. But what we do see is that
these therapies actually seem to work better
in these patients. This is a surprising
finding because we think that these patients
are immunosuppressed. We really equate obesity
with chronic inflammation and immune suppression. And so our initial
hypothesis, our expectation was that immunotherapies
would work less well in obese patients. But I think really where it
makes the biggest difference is that it shows us that when we’re
talking about immunotherapy and we’re looking
for biomarkers, we’ve looked a lot at
the tumor itself to try to find those biomarkers. But since these
treatments rely so heavily on the patient’s immune system,
what we’re seeing is that factors that really aren’t
factors off the tumor, but are factors of the patient
themselves– things like sex, age, obesity, previous exposure
to infections, et cetera– that all of these
things can affect the functioning of
the immune system and may also be
very good biomarkers for whether a patient
will or will not respond to cancer immunotherapy.

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