Abstract
Professional antigen-presenting cells (APCs), such as dendritic cells (DCs), are central to the initiation and regulation of anti-cancer immunity. However, in the immunosuppressive environment within a tumor APCs may antagonize anti-tumor immunity by inducing regulatory T cells (Tregs) or anergy of effector T cells due to lack of efficient costimulation. Hence, in an optimal setting, anti-cancer drugs have the power to reduce tumor size and thereby may induce the release of tumor antigens and, at the same time, modulate APC function toward efficient priming of antigen-specific effector T cells. Selected cytotoxic agents may revert APC dysfunction either by directly maturing DCs or through induction of immunogenic tumor cell death. Furthermore, specific cytotoxic agents may support adaptive immunity by selectively depleting regulatory subsets, such as Tregs or myeloid-derived suppressor cells. Perspectively, this will allow developing effective combination strategies with novel immunotherapies to exert complementary pressure on tumors via direct toxicity as well as immune activation. We, here, review our current knowledge on the capacity of anti-cancer drugs to modulate APC functions to promote durable anti-cancer immune responses.
Highlights
In the immunosuppressive environment within a tumor antigen-presenting cells (APCs) may antagonize anti-tumor immunity by inducing regulatory T cells (Tregs) or anergy of effector T cells due to lack of efficient costimulation
dendritic cells (DCs) are Central to the Initiation and Regulation of Anti-Cancer Immunity. Both the induction of endogenous anti-tumor immune responses and the successful implementation of immunotherapy protocols rely on adequate activation of adaptive immunity by antigen-presenting cells (APCs)
Tumor cells differ from normal cells due to expression of altered-self or neo-antigens that arise as a consequence of genetic instability and high mutation rates in transformed cells [7, 8]
Summary
Received: 23 April 2015 Accepted: 14 September 2015 Published: 29 September 2015. Citation: Martin K, Schreiner J and Zippelius A (2015) Modulation of APC function and anti-tumor immunity by anti-cancer drugs. Professional antigen-presenting cells (APCs), such as dendritic cells (DCs), are central to the initiation and regulation of anti-cancer immunity. Specific cytotoxic agents may support adaptive immunity by selectively depleting regulatory subsets, such as Tregs or myeloid-derived suppressor cells. This will allow developing effective combination strategies with novel immunotherapies to exert complementary pressure on tumors via direct toxicity as well as immune activation. Here, review our current knowledge on the capacity of anti-cancer drugs to modulate APC functions to promote durable anti-cancer immune responses Both the induction of endogenous anti-tumor immune responses and the successful implementation of immunotherapy protocols rely on adequate activation of adaptive immunity by antigen-presenting cells (APCs). Expression of T cell-directing cytokines and additional costimulatory surface receptors by DCs subsequently provides the impulse for appropriate
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