After many years that
traditional cancer therapies, such as surgery, chemotherapy and radiotherapy,
have been trying to attack directly cancer by destroying dividing cells or
removing solid cancers, immunotherapy emergence has provided a new weapon in
the fight against the disease by proposing the concept of targeting the immune
system, instead of the tumor itself 5.
several advantages over conventional therapies. Firstly, activated immune cells
are able to act on regions that are not accessible for a surgery, while even subtle
emergence of cancer could potentially be detected and targeted by the immune
system, if it had been adequately activated11. Despite the fact that
radiotherapy is more targeted than chemotherapy, it can also damage surrounding
healthy cells, while immunotherapy can specifically target tumors decreasing
the side effects. For instance, patients with non-small-cell-lung cancer (NSCLC),
who expressed PD1 in half of their cancer cells, responded efficiently to an a-PD1
therapy, manifesting reduced side effects in comparison to chemotherapy12.
Second, conventional therapies are not able to attack slowly dividing cancer
stem cells, as they mainly target rapidly proliferating cells. However, cancer
stem cells are considered to be responsible for the generation of tumors, recurrence
and metastasis due to their ability to be self-renewed and differentiated; their
elimination may be possible with immunotherapy13.
is capable of inducing long-term responses, at least in a subset of patients with
different types of cancer. Clinical trials have shown that treatment with
ipilimumab (IgG1 monoclonal antibody against CTLA-4) may achieve the survival
of patients up to 5 years after their diagnosis in already treated patients
with advanced melanoma and in untreated ones to 20% and 30%, respectively14.
In addition, nivolumab and lambrolizumab (IgG4 monoclonal antibody against PD-1)
seem to be even more efficient than ipilimumab in terms of durability and high
response rate 15,16. These results stress the significant
contribution of immunotherapy to the duration of the responses, which could be related
to the immunologic memory capable of delaying -if not avoiding due to cancer
editing- the recurrence of the tumor17. The effects of chemotherapy,
in contrast, are usually temporary and develop resistance to the majority of
There are also data revealing
that potent responses of chemotherapy or radiotherapy are potentially associated
with the immune response18,19. Although it was considered that
chemotherapy acted exclusively by hampering cell division of tumor cells and radiation therapy by
accumulating DNA damage in tumor cells and blocking in this way cell
proliferation, recent studies seem to associate the efficacy of these therapies
with the activation of the immune system18,19. More precisely, several
chemotherapeutics (such as anthracyclines, oxaliplatin, cyclophosphamide) and
radiotherapy can cause extensive non-specific apoptosis, called immunogenic
cell death, inducing immune response against dying cancer cells 20,21.
This also strengthens the notion that the immune system is necessary for an
efficient response against cancer.