However, in the context of diseases such as cancer, this stress-immunity cycle may become dysregulated since cancer cells manipulate various components of this cycle to fuel their own growth at the expense of the tissue and the organism (see Figure 1). Broadly speaking, on one hand, cancer cells dysregulate the normal cellular stress responses to re-orient them towards upholding cellular growth, while inhibiting cell death and enabling invasive or metastatic behaviour. On the other hand, cancer cells and the tumour severely dysregulate or inhibit various components of the immune system, both locally in the tumour as well as systemically, thereby compromising the ability of the immune cells to ameliorate the dysregulation of cellular stress responses (Figure 1). Accordingly, inhibition of cancer cell death, stress-signalling driven growth, immunosuppressive tumour immune landscape (especially anti-inflammatory macrophages), and induction of CD8+T cell dysfunction, are only a few of the many different processes that cancer cells exploit to disturb the cellular stress-immunity cycle to facilitate tumour growth and dissemination (Figure 1).

Conventional anticancer therapies have all strived to correct this dysregulation of the stress-immunity cycle by killing cancer cells and reduce tumour burden. Unfortunately, in past, these conventional anticancer therapies have achieved limited success in meaningfully prolonging the survival of patients. This is due to both primary and acquired resistance of cancer cells against these therapies as well as their inability to properly re-activate our immune system against (residual) cancer cells. However, a tremendous success in the pursuit to prolong cancer patient’s long-term survival has been achieved over the last decade, due to the development of cancer immunotherapy. Several immunotherapies are now available to clinicians and several more are in development. These include antibody-based, T cell-based, and vaccine-based therapies. Although such approaches have had great successes yet not all cancer patients or cancer types respond to current immunotherapies. This indicates that we still lack sufficient understanding of the tumoral dysregulation of stress-immunity cycle and its immunotherapeutic or cancer cell-level therapeutic vulnerabilities.

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Our CSI Lab aims to comprehensively dissect this cellular stress-immunity cycle, in order to understand its homeostatic as well as dysregulated "avatars". Our lab aims to exploit this knowledge to improve immunotherapy of hard-to-treat cancer types (e.g., brain cancer, colorectal cancer, kidney cancer), guided by high precision immune-biomarkers.