Radiotherapy and chemotherapy can potentially serve a
new goal: improve the efficacy of immunotherapy for cancer
patients. Researcher Inge Verbrugge and her colleagues from the
Netherlands Cancer Institute have published a paper about this
Cancer Immunology Research.
Immunotherapy is a promising new cancer therapy. It stimulates
the patient's own immune cells to recognize and kill tumor cells.
Unfortunately, not all patients respond to immunotherapy and
scientists are looking for ways to change this. Researcher Inge Verbrugge
and her colleagues at the Netherlands Cancer Institute discovered
that a specific combination of immunotherapy, radiotherapy and
chemotherapy is very effective against tumors that do not respond
to immunotherapy alone. They describe their findings in the
Cancer Immunology Research.
Attract and activate
The scientists were looking for a way to boost the immune cells.
When immune cells encounter something foreign, such as a virus or a
tumor, they will usually proliferate and kill it. Immunotherapy
with checkpoint inhibitors can help the immune cells to kill cancer
video explains how these drugs work). However, this treatment
is not effective in all patients, partly because not every tumor
attracts and activates many immune cells.
Under supervision of Inge Verbrugge
Jannie Borst researchers Paula Kroon, Elselien
Frijlink and colleagues investigated a strategy for inducing an
effective immune response against these tumors as well. In mice
with cancer they combined a checkpoint inhibitor with a different
form of immunotherapy (anti-CD137 antibody) and added radio- and/or
low-dose chemotherapy on top of this (see illustration). The second
form of immunotherapy was able to help induce an immune response,
however this was not sufficient to kill the tumor. The idea behind
adding radiotherapy is that the cells that die because of it can
help induce an immune response, and the surviving cells are more
sensitive to the immune attack. A low-dose of chemotherapy can also
make tumor cells more sensitive to elimination by immune cells.
In tumor cells that are resistant to immunotherapy with
checkpoint inhibitors, radiotherapy and chemotherapy can synergize
with a specific immunotherapy combination to induce tumor cell
death. The checkpoint inhibitor (red Y) 'removes the brake' on the
immune cells (T cells) and the other form of immunotherapy (an
antibody to CD137, green Y) 'presses the gas pedal' on the immune
cell. Radiotherapy and chemotherapy enable the activated immune
cells to kill the tumor cells (shriveled purple cells).
Indeed, the combination of these four treatment modalities
proved to be very efficient in mice. The newly raised immune cells
did a better job and the mice survived longer. The immune cells
even cleared tumor cells that resided outside the irradiated
tissue. In the future, chemo-radio-immunotherapy may contribute to
improving the survival of patients with tumors that do not respond
well to immunotherapy with checkpoint inhibitors.
Researchers of the Netherlands Cancer Institute are already
studying this concept in several patient cohorts. The PEMBRO-RT
trial combines radiotherapy with checkpoint inhibition in patients
with lung cancer. The TONIC-trial investigates to what extend
radiotherapy and chemotherapy can improve the efficacy of
checkpoint inhibitors in breast cancer patients.
Read the scientific article
This research was financed by the Dutch Cancer Society and