Journal Article

The secret ally: immunostimulation by anticancer drugs

Zitvogel, Laurence, Galluzzi, Lorenzo, Senovilla, Laura, Kroemer, Guido

2012

Overview

Key Points Throughout the past century, conventional anticancer chemotherapeutics have been used based on their ability to selectively kill neoplastic cells while sparing their normal counterparts. More recently, targeted anticancer agents have been developed following the identification of cancer cell-specific molecular targets. The classical notion that cancer constitutes a cell-autonomous genetic disease has progressively been invalidated, along with the understanding that the tumour microenvironment (including stromal and immune components) is a crucial determinant for tumour progression and response to therapy. Local and systemic indicators of an ongoing response as well as biomarkers that predict the propensity of the immune system to engage in an anticancer immune response have been correlated with therapeutic outcome. Several conventional and targeted anticancer chemotherapeutics can induce tumour-specific immune responses, either by triggering immunogenic cancer cell death or by eliciting innate or cognate immune effector mechanisms. Conventional chemotherapeutics and targeted agents ameliorate the efficacy of several types of anticancer immunotherapy, including vaccination approaches and cytokine-mediated immunostimulation. Immunochemotherapy currently appears to be a promising strategy for the eradication of cancer. It can be anticipated that the elucidation of the intricate crosstalk among cancer, stromal cells and immune cells will provide additional targets for anticancer therapy. A crucial role of the immune system in cancer progression and response to therapy has recently emerged. Here, Galluzzi and colleagues discuss the immune parameters that may predict the therapeutic response of patients to chemotherapeutics, and review the mechanisms by which current antineoplastic agents activate the immune system against cancer. It has recently become clear that the tumour microenvironment, and in particular the immune system, has a crucial role in modulating tumour progression and response to therapy. Indicators of an ongoing immune response, such as the composition of the intratumoural immune infiltrate, as well as polymorphisms in genes encoding immune modulators, have been correlated with therapeutic outcome. Moreover, several anticancer agents — including classical chemotherapeutics and targeted compounds — stimulate tumour-specific immune responses either by inducing the immunogenic death of tumour cells or by engaging immune effector mechanisms. Here, we discuss the molecular and cellular circuitries whereby cytotoxic agents can activate the immune system against cancer, and their therapeutic implications.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 53 / 631/154/436/2388 / 631/250 / 631/67/1059 / 67 / Animals / Antigens, Neoplasm - immunology / Antimitotic agents / Antineoplastic agents / Antineoplastic Agents - pharmacology / Antineoplastic Agents - therapeutic use / Antitumor agents / Biomedical and Life Sciences / Biomedicine / Biotechnology / Cancer / Cancer Research / Cancer Vaccines - immunology / Cancer Vaccines - therapeutic use / Care and treatment / Colorectal cancer / Cytotoxic agents / Development and progression / Gene polymorphism / Genes / Health aspects / Humans / Immune response / Immunization / Immunization - methods / Immunization - trends / Immunogenicity / Immunomodulation / Immunostimulation / Medicinal Chemistry / Microenvironments / Molecular Medicine / Neoplasms - drug therapy / Neoplasms - immunology / Neoplasms - prevention & control / Pharmacology/Toxicology / review-article / Tumors