Predicting Immunotherapy Outcomes in Glioblastoma Patients through Machine Learning.

ABSTRACT

Glioblastoma is a highly aggressive cancer associated with a dismal prognosis, with a mere 5% of patients surviving beyond five years post diagnosis. Current therapeutic modalities encompass surgical intervention, radiotherapy, chemotherapy, and immune checkpoint inhibitors (ICBs). However, the efficacy of ICBs remains limited in glioblastoma patients, necessitating a proactive approach to anticipate treatment response and resistance. In this comprehensive study, we conducted a rigorous analysis involving two distinct glioblastoma patient cohorts subjected to PD-1 blockade treatments. Our investigation revealed that a significant portion (60%) of patients exhibit persistent disease progression despite ICB intervention. To elucidate the underpinnings of resistance, we characterized the immune profiles of glioblastoma patients with continued cancer progression following anti-PD1 therapy. These profiles revealed multifaceted defects, encompassing compromised macrophage, monocyte, and T follicular helper responses, impaired antigen presentation, aberrant regulatory T cell (Tregs) responses, and heightened expression of immunosuppressive molecules (TGFB, IL2RA, and CD276). Building upon these resistance profiles, we leveraged cutting-edge machine learning algorithms to develop predictive models and accompanying software. This innovative computational tool achieved remarkable success, accurately forecasting the progression status of 82.82% of the glioblastoma patients in our study following ICBs, based on their unique immune characteristics. In conclusion, our pioneering approach advocates for the personalization of immunotherapy in glioblastoma patients. By harnessing patient-specific attributes and computational predictions, we offer a promising avenue for the enhancement of clinical outcomes in the realm of immunotherapy. This paradigm shift towards tailored therapies underscores the potential to revolutionize the management of glioblastoma, opening new horizons for improved patient care.