Cancer is one of the leading causes of death worldwide, and current research has
focused on the discovery of novel approaches to effectively treat this disease. Recently, a considerable
number of clinical trials have demonstrated the success of immunomodulatory
therapies for the treatment of cancer. Monoclonal antibodies can target components of the
immune system to either i) agonise co-stimulatory molecules, such as CD137, OX40 and
CD40; or ii) inhibit immune checkpoints, such as cytotoxic T-lymphocyte-associated antigen
4 (CTLA-4), programmed cell death-1 (PD-1) and its corresponding ligand PD-L1. Although
tumour regression is the outcome for some patients following immunotherapy, many patients
still do not respond. Furthermore, chemotherapy has been the standard of care for most cancers,
but the immunomodulatory capacity of these drugs has only recently been uncovered.
The ability of chemotherapy to modulate the immune system through a variety of mechanisms,
including immunogenic cell death (ICD), increased antigen presentation and depletion
of regulatory immune cells, highlights the potential for synergism between conventional chemotherapy
and novel immunotherapy. In addition, recent pre-clinical trials indicate dipeptidyl
peptidase (DPP) enzyme inhibition, an enzyme that can regulate immune cell trafficking to
the tumour microenvironment, as a novel cancer therapy. The present review focuses on the
current immunological approaches for the treatment of cancer, and summarizes clinical trials
in the field of immunotherapy as a single treatment and in combination with chemotherapy.
PD-L1 and B7-1 Cis-Interaction: New Mechanisms in Immune Checkpoints and Immunotherapies