Work investigating germline influences on thyroid-related adverse events for patients on cancer immunotherapy is now in press, lead by Jia Luo and Tori Martucci in collaboration with the labs of Melinda Aldrich, Matt Hellmann, and Elad Ziv:

Immunotherapy-Mediated Thyroid Dysfunction: Genetic Risk and Impact on Outcomes with PD-1 Blockade in Non–Small Cell Lung Cancer.
Luo J, Martucci VL, Quandt Z, Groha S, Murray MH, Lovly CM, Rizvi H, Egger JV, Plodkowski AJ, Abu-Akeel M, Schulze I, Merghoub T, Cardenas E, Huntsman S, Li M, Hu D, Gubens MA, Gusev A[+], Aldrich MC[+], Hellmann MD[+], Ziv E[+]. Clin Cancer Res. 2021

This study demonstrated a significant association across three cohorts between (a) germline risk for a complex phenotype (thyroid conditions and use of thyroid medication) in a non-cancer setting and (b) thyroid dysfunction / adverse events brought on by immunotherapy in lung cancer patients. This work adds to a growing body of literature showing that cancer immunotherapy is influenced by common germline variation, and is a preview of how germline risk scores could be leveraged to understand the mechanisms of cancer outcomes more broadly.

Figure: Kaplan-Meier plot of time to thyroid adverse event stratified on germline risk score in two independent cohorts.

schematic