Profiling TILs to Advance Our Understanding the Host Immune Response
Many new cancer therapies are immune-modulatory, including immunotherapies and targeted therapies, cancer vaccines, and cellular therapeutics like adoptive T-cell therapy. Immune molecular biomarkers are needed to reliably predict response to these new treatment modalities. The accurate assessment of tumor infiltrating lymphocytes (TILs) is emerging as a potential clinically actionable cancer biomarker.
Immunohistochemistry (IHC) is likely still the most common technology for assessing TILs. While IHC is evolving, including the use of multiplexed, quantitative IHC, it still only provides a two dimensional view of TILs that are present in a sliver of tissue. This makes the results heavily dependent on the location of each tumor section sampled.
In contrast, the advent of immunosequencing as a relatively new technology uses gDNA extracted from tumor tissue to provide a quantitative, molecular assessment of the thousands of T-cell receptor (TCR) sequences that make up the TILs in a given tissue sample. Immunosequencing provides both the absolute TIL count and TIL density. Unique to immunosequencing is the ability to measure TIL clonality, which measures the frequency distribution of the TCR repertoire as a functional read out of TIL proliferation and expansion. Recent studies have repeatedly shown that TIL clonality may be a better predictor of outcomes than TIL counts alone. This is one of the primary factors driving the adoption of the immunoSEQ® Assay in solid tumor research.
The immunoSEQ Assay is being used to inform prognosis and improve staging of solid tumors. Preliminary data indicates that the number of TILs and the diversity of the TIL population positively correlate to outcomes, including overall survival.
The immunoSEQ Assay is being incorporated in clinical trials to evaluate and predict responses to therapies and inform smart drug combinations and sequential therapies. For example, not all individuals initially respond to checkpoint inhibitors. The immunoSEQ Assay can identify patients with low TIL density and low clonality, who may be less likely to respond to checkpoint inhibition upfront. These patients may benefit from an initial therapy to prime their immune system, increasing the chances that checkpoint inhibition will be successful.
Lastly, in drug development, sequencing TCRs, can help elucidate the mechanism of action of certain compounds and find answers to many questions related to T-cell populations in the tumor microenvironment. The immunoSEQ Assay can also be used to predict adverse side effects due to systemic responses and to identify the optimal dose for certain immunomodulatory compounds.
In the immunological response to cancer, lymphocytes play a critical role in attacking and killing tumors. Using the immunoSEQ Platform to profile TILs is bringing new insights to a wide variety of solid tumor research by helping advance our understanding of the host immune response.