How Cancers Escape Immune Destruction and Mechanisms of Action for the New Significantly Active Immune Therapies: Helping Nonimmunologists Decipher Recent Advances

Abstract

With the Food and Drug Administration and other worldwide regulatory authorities' approval of ipilimumab (Yervoy), sipuleucel-T (Provenge), nivolumab (Opdivo), and pembrolizumab (Keytruda), oncologic therapy has now moved into noncancer cell targets within the immune system. For many nonimmunologists, understanding how these vastly different therapies work to improve survival, like no other therapies have in the past, is a challenge. The present report reviews the normal function of the immune system, how cancers escape the normal immune system, and how these new therapies improve immune system reactions against cancers. The Oncologist 2016;21:233-243 Implications for Practice: Oncologists have tremendous experience with therapies that target the cancer cells. New biologic agents have been rapidly introduced recently that target not cancer cells, but the patient's immune cells. The mechanisms of action of these immune-based biologic agents are within the host immune system.To understand these new biologic therapies, basic knowledge of normal and abnormal immune function is essential. The present report explains the up-to-date basic immune normal and abnormal function and prepares the oncologist to understand how the new drugs work, why they work, and why there are associated adverse events.

Effect of Gender on the Outcome of Patients Receiving Immune Checkpoint Inhibitors for Advanced Cancer: A Systematic Review and Meta-Analysis of Phase III Randomized Clinical Trials

“…Overall, our meta-analysis differs from The emerged evidence for the lack of efficacy of anti-CTLA-4 in women invites critical interpretation. The renowned gender-related differences in immune response [13] and the different mechanisms of action of anti-CTLA-4 and anti-PD-1/ PDL-1 [49,50] may help provide a biologic rationale to this finding.…”

“…CTLA-4 is expressed on T lymphocytes and, by binding B7 receptors on antigen-presenting cells (APCs), determines inhibition of T-cell activation at the priming phase of the immune response, when a naïve T lymphocyte recognizes tumor antigens for the first time [49]. Therefore, anti-CTLA-4 antibodies can re-activate suppressed T lymphocytes, stimulating their proliferation and triggering humoral and cytotoxic anti-tumor response.…”

Urgent need to define Pretreatment predictors of immune check point inhibitors related endocrinopathies: A case report and review of literature

“…Inhibition of these 2 pathways leads to an increased activation of the immune system, which may be used against the cancer cells. [6,7] A series of checkmate trials have led to the accelerated approval of these immune check point inhibitors in the treatment of metastatic melanoma, renal cell cancer, non-small cell lung cancer, small cell cancer and urothelial cancer. [8][9][10][11][12][13][14] Also, its use in the treatment of hepatocellular cancer is under an expedited review by FDA.…”

A stochastic individual-based model to explore the role of spatial interactions and antigen recognition in the immune response against solid tumours

“…Immune cells, specifically dendritic cells (DCs) and cytotoxic T lymphocytes (CTLs), detect and target solid tumours through recognising and processing the small peptides (i.e. the antigens) that are expressed by tumour cells (Messerschmidt et al, 2016). The antigenic composition of solid tumours can be heterogeneous, whereby each cell within the tumour mass may have an antigen profile characterised by different expression levels of tumour antigens.…”

“…Cell-cell interactions involved in the immune response to cancer depend upon the spatial position of both immune cells and tumour cells within the tumour micro-environment (Chaplin, 2010;Messerschmidt et al, 2016). In particular, as a result of tumour growth, cells within the tumour can become more exposed to immune action depending on their location in relation to other cells of the tumour micro-environment (Hanahan and Weinberg, 2011).…”