Biomarkers in Cancer Immunotherapy

Abstract

Antibodies against T cell checkpoint molecules have started to revolutionize cancer treatment. Nevertheless, less than half of all patients respond to these immunotherapies. Recent work supports the potential value of biomarkers that predict therapy outcome and inspires the development of assay systems that interrogate other aspects of the cancer-immunity cycle.

Immunity, inflammation, and cancer: an eternal fight between good and evil

“…In recent years, tumor immunologists and practicing oncologists have seen a dream come true with the clinical implementation and regulatory approval of cancer immunotherapies (43). It was first suggested by Paul Ehrlich, 50 years after Virchow, that the immune system can fight tumors (44), a suggestion reiterated by the immunosurveillance hypothesis of Burnet and Thomas (45).…”

“…It is the elevated expression of negative regulatory signals and the presence of immunosuppressive cells that account for establishment of immune tolerance in such cancers. However, while immune checkpoint blockade and adoptive T cell transfer strategies can result in a clinical benefit in a subset of patients, most patients are still refractory to such therapies (43,54,55). Thus, future effort should be directed toward increasing response rates and expanding the applicability of immunotherapy to all types of cancer.…”

Analysis of Major Histocompatibility Complex (MHC) Immunopeptidomes Using Mass Spectrometry*

“…Notably, the detection of tumor-specific mutant MHC peptides has not been achieved yet using DIA MS. If tested and validated, DIA MS could, nevertheless, represent a robust approach in the clinic for the development of next-generation T-cell-based cancer vaccines as well as for the stratification of patients who might best benefit from checkpoint blockade immunotherapy (138,145,146).…”

Structure of the Complex of Human Programmed Death 1, PD-1, and Its Ligand PD-L1

“…One of the mechanisms of that suppression involves interference with immunologic checkpoints (inhibitory receptors) on immune cells like, for example, the programmed death receptor 1 (PD-1), whereby cancer cells present negative immunologic regulators inducing exhaustion (loss of function) of antigen-specific effector T cells (Phan et al, 2015; Herbst et al, 2014; Topalian et al, 2015). A recent major breakthrough in cancer immunotherapy has emerged in immunologic checkpoint blockade, utilizing antibodies masking the inhibitory receptor PD-1 on immune effector cells or PD-1 inhibitory receptor ligand (PD-L1) on tumor cells, thereby alleviating cancer-induced immunosuppression (Herbst et al, 2014; Schumacher et al, 2015). This represents a major paradigm shift whereby the therapy aims at disinhibition of native immune response compared with previous approaches whereby tumor vaccines and recombinant cytokines aimed at its de novo activation.…”