Immunogenic cell death (ICD) in the cancer-immune dialogue

Introduction

The success of most, if not all, anticancer treatments depends on the (re)activation of immunosurveillance. This has been documented for several therapeutic modalities, not only immunotherapy but also chemotherapy, targeted therapy, and radiotherapy.

Immunogenic Cell Death

In response to antineoplastic drugs, malignant cells can undergo immunogenic cell death (ICD). This process exposes and releases danger signals that act on pattern recognition receptors expressed by immune cells, particularly dendritic cells (DCs). This interaction triggers the first steps of a therapeutically relevant anticancer immune response.

Objectives

Based on solid preliminary data and novel methodological approaches, we propose the following objectives:

1. Objective 1: Obtain fundamental insights into the physicochemical properties and molecular mode of action of pharmacological ICD inducers.
2. Objective 2: Create chemical-genetic systems for synthetic ICD induction to study ICD effects on the immune system without perturbation by pleiotropic anticancer drugs.
3. Objective 3: Identify new ICD-relevant immune checkpoints acting at the level of DCs.
4. Objective 4: Use this knowledge to generate an integrated view of the cancer-immune dialogue ignited by malignant cells succumbing to ICD and DCs perceiving ICD, hence developing optimal strategies for the stimulation of tumor immunosurveillance.

Clinical Relevance

The concept of ICD has already been useful for patient-relevant biomarker discovery, drug development, and trial design. This strongly suggests that a deeper exploration of this phenomenon will yield clinically relevant information.