Clinical and biological risk factors associated with clinical outcomes of immune-checkpoint inhibitor therapy

Abstract

Immune-checkpoint inhibitors (ICIs) are a novel therapeutic approach to invigorate the antitumour response by inhibiting the activity of inhibitory checkpoint molecules. ICIs can significantly strengthen the cancer-specific cytotoxic T cell response, resulting in improved tumour destruction, used alone or in combination with other anti-cancer agents, such as chemotherapy, biological and/or targeted therapies. In some cancers this combinatorial approach can achieve a durable response, even in metastatic settings, increasing survival of patients previously considered as only eligible for palliative care.
Although ICIs share a similar mechanism of action, inhibition of checkpoint signalling does not always lead to a favourable response and/or disease regression, as different agents can demonstrate significantly different efficacy and safety outcomes. This study aimed to uncover both clinical and biological factors impacting the outcomes of ICI therapy. Through comprehensive analyses, several factors were pinpointed, offering insights into the potential markers for predicting the clinical outcomes of ICI therapy. Nonetheless, it's important to emphasise that the significance of these markers in forecasting ICI therapy outcomes needs further clarification in larger clinical trials.
Finally, successful validation of the preliminary findings will not only deepen our understanding of the molecular mechanisms that drive toxicity and response following ICI therapy but also has the potential to refine ICI-based therapeutic strategies on a broader scale. Biomarker discovery holds significant promise to enhance both patient survival rates and quality of life, as well as tailoring personalised approaches in immuno-oncology.

Date of Award	2024
Original language	English
Awarding Institution	Western Sydney University
Supervisor	Golo Ahlenstiel (Supervisor)