Cancer immunotherapy: the beginning of the end of cancer?

Abstract

These are exciting times for cancer immunotherapy. After many years of disappointing results, the tide has finally changed and immunotherapy has become a clinically validated treatment for many cancers. Immunotherapeutic strategies include cancer vaccines, oncolytic viruses, adoptive transfer of ex vivo activated T and natural killer cells, and administration of antibodies or recombinant proteins that either costimulate cells or block the so-called immune checkpoint pathways. The recent success of several immunotherapeutic regimes, such as monoclonal antibody blocking of cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD1), has boosted the development of this treatment modality, with the consequence that new therapeutic targets and schemes which combine various immunological agents are now being described at a breathtaking pace. In this review, we outline some of the main strategies in cancer immunotherapy (cancer vaccines, adoptive cellular immunotherapy, immune checkpoint blockade, and oncolytic viruses) and discuss the progress in the synergistic design of immune-targeting combination therapies.

The immune microenvironment of HPV-negative oral squamous cell carcinoma from never-smokers and never-drinkers patients suggests higher clinical benefit of IDO1 and PD1/PD-L1 blockade

“…While the mutational load may contribute to the clinical response to immunotherapy through neo-antigen-specific T cell responses, this is not always the case [27]. HPV-positive HNSCC harbor fewer mutations [28] and present a higher response to anti-PD1 when compared to HPV-negative HNSCC [14,15,29].…”

Lymphatic vessel density is associated with CD8+ T cell infiltration and immunosuppressive factors in human melanoma

“…1-4 Despite the promotion of tumor antigen specific T cell responses by active immunization, checkpoint blockade or adoptive transfer, only a subset of patients experience clinical benefit. 5 In melanoma, recent studies have sought predictive indicators (genetic or phenotypic) by comparing patients who respond to immunotherapies with those that do not.…”

Serum levels of soluble programmed death protein 1 (sPD-1) and soluble programmed death ligand 1 (sPD-L1) in advanced pancreatic cancer

“…5,6 Almost a decade ago, checkpoint blockade targeting the programmed death protein 1/programmed death ligand 1 (PD-1/PD-L1) pathway was described as a promising therapeutic target in PC and has been proven to be successful in a variety of other solid tumor entities. [7][8][9] While the importance of PD-L1 in PC immune evasion was confirmed very recently, only preliminary -rather disappointing -data on the potential efficacy of PD-1/PD-L1 blockade is available in PC yet. [10][11][12] High levels of soluble plasma PD-L1 (sPD-L1) were described as an adverse prognostic factor in several malignancies susceptible to PD-1/PD-L1 blockade, including renal cell cancer and hepatocellular carcinoma (HCC).…”