Identifying immunological, metabolome- and microbiome- based parameters influencing efficacy of immuntherapy in kidney cancer patients

Martin Pichler, Division of Oncology, Department of Internal Medicine, Medical University of Graz, Austria

Background:
The treatment landscape in uro-genital cancers including renal cell carcinoma (RCC) has been
significantly changed through the introduction of immunotherapy. Despite these new treatment
options, the response rates with these agents range between 42 to 71 % in RCC. Thus, much
space for improving the efficacy of these cost-intensive and potentially toxic drugs is still left
and a better understanding of predictive and influential factors might help to improve the clinical
outcome. Recent work indicated that the gut microbiome might influence the response of
immunotherapy in melanoma and beyond other types of cancer. Other factors such as immune
cell subtypes, cytokines or metabolites might also influence the efficacy of immunotherapy in
genito-urogential cancers.

Hypothesis and Objectives:
In this project we aim to adress the following hypothesis:
• Non-eubacterial microorganisms (archaea) in the gut microbiome correlate with treatment
re-sponse, progression free survival and overall survival of patients treated immunotherapy
across different urogenital cancers.
• Microbiom-associated metabolites and immunological blood-based cellular and humoral
factors, identified in the patient blood and stool, correlate with treatment response, progression
free survival and overall survival of patients treated with immunotherapy across different
urogenital cancers.

Methodology:
Investigator-initiated trial design, Biostatistical Analysis of longitudinal data, untargeted NMR-
spectroscopy, Microbiome profiling, amplicon sequencing, immune cell and parameter
measurement

References:
Patterns of Peripheral Blood B-Cell Subtypes Are Associated With Treatment Response in
Patients Treated With Immune Checkpoint Inhibitors: A Prospective Longitudinal Pan-Cancer
Study.Barth DA, et al. Front Immunol. 2022 Apr 1;13:840207
Gut microbes as biomarkers of ICI response - sharpening the focus.
Bhutiani N, Wargo JA. Nat Rev Clin Oncol. 2022 Aug;19(8):495-496. doi: 10.1038/s41571-
022-00634-0