This proposal addresses PQ2: How do variations in immune function caused by
comorbidities or observed among different populations affect response to cancer
While the role of the immune system in controlling and eradicating tumors has
been known for decades, it is only in the past few years that immunotherapy has emerged
as a clinically viable way to target cancer. Little is known about how the immune response
differs between populations defined by gender and ethnicity, either in terms of levels of
immune infiltration or the intrinsic functionality of specific immune cell types.
We are developing resources and methods to dissect the impact of levels of
infiltrating leukocytes on cancer outcomes. PRECOG is a large compendium of gene
expression datasets comprising nearly 40,000 patient samples across 39 distinct cancer
histologies, for which overall survival information (and other outcomes) is available.
Previously we used PRECOG to assess the influence of immune cell levels on overall
survival, identifying commonalities and differences across cancer. Many of these
associations were therapy-independent, emphasizing how the immune system is a critical
component of patient response even in the context of standard chemotherapy.
Here we will extend PRECOG to incorporate information on patient gender and
ethnicity. No published studies have systematically analyzed similarities and differences
in the impact of immune cell types on clinical outcomes in these groups. Here we identify
how infiltrating immune levels vary between tumors from different populations, and how
they differentially affect responses to specific therapies as well as overall survival. This
will generate testable hypotheses regarding variations in immune infiltration and function
between populations. These will also be associated with response to specific therapies,
and with overall survival. Using novel deconvolution approaches we will further dissect
immune function in relation to survival and therapy response. This prognostic map will
illuminate similarities and differences across the landscape of cancer populations and will
be a powerful new resource for the cancer immunologic community.
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