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mirrors a subset of that in humans, suggesting that these preclinical models accurately recapitulate a subset of human disease. Elevated expression in mice and humans Given the
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compartments, suggesting that these immune Axis likely plays a huge role in cellular these represent a small subset of the figures, may be consistent with the observed lack of clinical

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observed population profiles in most tumors, suggesting the presence of recently activated proliferating and non-senescent intratumoral cells with potential for therapeutic rejuvenation.

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Figure Thumbnail Figure Figure Human Contains Exhausted Show Full Caption View Larger Image Figure Browser Download High Resolution Image Download Next, we studied

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dysfunction in the context of this disease. Humans contain a similarly depleted intratumoral cell population To investigate whether these observations could be extended to humans, we

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tumors. Progenitor cell-like has been shown Evidence is the basis for the proliferative burst in the blocking response Miller et al., Siddiqui et al. What we observed in most tumors, but

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maps and, consistent with our clinical consistent with the previous analysis. with our mouse model Consistently, we observed that eventually exhausted graphs are present in most

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isolated intratumoral cells from freshly resected surgical samples for flow cytometry analysis. Of the samples evaluated, 4 had sufficient range for further immunophenotyping. Consistent

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with previous reports by Stromness et al., most – is maps, reflecting prior antigenic experience, a large fraction of intratumoral cells co-express multiple co-inhibitory receptor

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Chihara et al., Schittinger et al., we examined co-inhibitory receptor expression on observed clusters had higher gene expression profiles associated with cellular depletion. Then we

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apply the cell Performing Gene Module Scores from Mice from Acute and Chronic but showed signs of cellular dysfunction. exhausted. This may reflect non-tumor-reactive

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interestingly also 'Chronic Effector' signature maps. Cells in the two smaller clusters and showed higher expression of naive memory markers, likely reflecting one or more abnormal

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