Molecular immune signatures of T-cell infiltration in cancer
- Author(s): Levy, Eric Daniel;
- Advisor(s): Ohno-Machado, Lucila;
- Harismendy, Olivier
- et al.
There is currently a strong interest in cancer research to profile the tumor- immune microenvironment to understand the complicated interplay of immune targeting and escape. With the recent developments of immune checkpoint inhibitors, which overcome the defenses cancer cells develop to prevent the immune system from targeting them, there has been an increasing importance in furthering our understanding of patients’ immune systems and the infiltration into tumors to lead to further breakthroughs in therapy.
Here, we develop and apply an analysis framework designed to characterize the tumor immune microenvironment through the identification of markers of T-cell infiltration in tumor tissue. This allows us to re-analyze a large public dataset of tumor sequencing data, The Cancer Genome Atlas, in order to evaluate and characterize markers of infiltrating T-cells across multiple cancer types.
First, we use a targeted deep sequencing approach as a validation to prove the accuracy of extracting T-cell markers from genome-wide tumor data. Then, we use our approach to identify and analyze T-cell infiltration across breast cancer samples, and evaluate their correspondence with other makers of immune infiltration and prognostic value. Finally, we extend our analysis methodology to 10,084 tumors from 28 cancer types, in order to evaluate differences in molecular markers of immune infiltration between these cancer types.
This work adds to the set of methodologies that can be used to profile immune infiltration in tumor samples, and highlights a new molecular marker for T-cell infiltration. This framework can be used in future studies that use deeper sequencing and experimental designs that generate the data to evaluate more thoroughly questions of immune infiltration compared to cancer progression and treatment. Using the methods developed here, the profiling of molecular markers of T-cell infiltration will further our understanding of the interaction between the immune system and tumors.