New tool identifies which cancer patients are most likely to benefit
from immunotherapy

Date:
August 27, 2020
Source:
University of Bath
Summary:
A new diagnostic tool that can predict whether a cancer patient
would respond to immunotherapy treatment has been developed. This
advance in precision medicine will allow clinicians to tailor
treatments specifically to patients and avoid treatment paths that
are unlikely to be successful.



FULL STORY ==========================================================================
A new diagnostic tool that can predict whether a cancer patient would
respond to immunotherapy treatment has been developed by scientists at
the University of Bath. This advance in precision medicine will allow clinicians to tailor treatments specifically to patients and avoid
treatment paths that are unlikely to be successful.


========================================================================== Immunotherapy is a type of cancer treatment that helps a patient's
immune system fight cancer and is having a profoundly positive impact
on cancer treatments. Cancers evade detection by the immune system,
making themselves invisible to the natural anti-tumour response and
actively blocking it.

One type of immunotherapy, called immune checkpoint inhibitors, are
antibodies that remove the brakes which the tumour has applied to the
immune system. This re-activates the patients' natural anti-cancer
response, which then destroys the tumour.

Whilst checkpoint inhibitor immunotherapy is very successful in some
patients, in others it has little or no effect. Given the inherent
toxicity risks in these treatments, there has been a growing need to
define which patients are most likely to benefit, avoiding unnecessary
exposure to those who will not.

Researchers in Bath led by Professor Banafshe' Larijani Director of
the Centre for Therapeutic Innovation (CTI-Bath), working with other
colleagues and the company FASTBASE Solutions Ltd, have now developed a prognostic tool using an advanced microscopy platform that identifies
immune cell interactions with tumour cells and also reports on the
activation status of immune-checkpoints that dampen the anti-tumour
response.

The team published its findings in Cancer Research, a journal of the
American Association for Cancer Research.



==========================================================================
The team studied an immune checkpoint consisting of two proteins termed
PD-1 (present on immune cells called T lymphocytes) and PD-L1 (present
on other types of immune cells and on the surface of many different
types of tumours).

Ordinarily, when PD-1 on the surface of T lymphocytes engages with
PD-L1 on the surface of other immune cells, it effectively switches
off the immune function of the T cell. In a healthy individual, these checkpoints tightly regulate the body's immune response, acting as an off-switch to prevent autoimmune and inflammatory disease.

Tumour cells essentially hijack this mechanism by expressing PD-L1 on
their surface enabling them to activate PD-1 on the T lymphocyte, thus switching off its anti-tumour function, allowing survival and the growth
of the tumour.

Immunotherapy checkpoint inhibitors work by disrupting the interaction
between the PD-L1 on the tumour and PD-1 on the T cell, and thus
re-establish the patient's anti-tumour activity.

This new tool determines the extent of PD-1/PD-L1 interaction in a biopsy
of the tumour, predicting whether the checkpoint inhibitor therapy is
likely to have significant clinical benefit. The ground-breaking results
show that immunotherapy-treated patients (with metastatic non-small
cell lung cancer) displaying a low extent of PD-1/PD-L1 interaction,
show significantly worse outcome than those with a high interaction.



========================================================================== Professor Larijani explained: "Currently, decisions on whether to
proceed with checkpoint inhibitor treatment are based simply on whether
PD-1 and PD-L1 are present in biopsies, rather than their functional
state. However our work has shown it is far more important to know that
the two proteins are actually interacting and therefore likely to be
having a functional impact on tumour survival." Professor Jose' I Lo'pez,
from the Department of Pathology, Cruces University Hospital (Bilbao,
Spain) and co-author of this study, said: "Immune checkpoint blockade
is becoming a therapeutic milestone in some cancers in the last years.

"Patients are selected for this treatment option using
immunohistochemistry, however, this technique does not reliably detect
all of the candidates that would potentially benefit. Actually, up
to 19% of patients supposedly negative do respond to this therapy."
Professor Stephen Ward, Vice-Chair of CTI-Bath and a co-author of the
study, said: "The tool we have developed is an important step towards personalised medicine. By using it, we can precisely select who will
benefit from immunotherapy.

"It will also show which patients are unlikely to respond well before
they start a long course of treatment, and these patients can be offered
a different treatment route.

"It should make treatment with these expensive biotherapeutics much
more efficient for the NHS." Dr Eunate Arana, Scientific Coordinator
of BioCruces Health Research Institute, said: "We find this technology
and its application in the field of immunotherapy truly interesting.

"Therefore, we are going to carry out a clinical trial in three hospitals
of BioCruces and BioDonostia, the Basque Public Health network, that
will allow us to evaluate the predictive capacity of this quantitative
imaging platform, to improve patient stratification for lung cancer immunotherapy." The next steps are to implement this imaging platform
in national and international trials to assess how this quantitative
prognostic tool may be used as a companion diagnostic.


========================================================================== Story Source: Materials provided by University_of_Bath. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. Lissete Sa'nchez-Magraner, James Miles, Claire L. Baker,
Christopher J.

Applebee, Dae-Jin Lee, Somaia Elsheikh, Shaimaa Lashin, Katriona
Withers, Andrew G. Watts, Richard Parry, Christine Edmead, Jose
Ignacio Lopez, Raj Mehta, Antoine Italiano, Stephen G. Ward,
Peter J. Parker and Banafshe' Larijani. High PD-1/PD-L1 checkpoint
interaction infers tumor selection and therapeutic sensitivity
to anti-PD-1/PD-L1 treatment. Cancer Research, 2020 DOI:
10.1158/0008-5472.CAN-20-1117 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/08/200827101824.htm

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