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Fig. 4 | Genome Medicine

Fig. 4

From: Transfer learning between preclinical models and human tumors identifies a conserved NK cell activation signature in anti-CTLA-4 responsive tumors

Fig. 4

ProjectR recovers conserved immunotherapy response in intratumoral NK cells from independent human melanoma scRNA-seq datasets. A Box plot of projected pattern 7 weights across intratumoral NK cells from metastatic melanoma patients prior to ICI treatment [5]. Cells are colored by therapy and separated by patient response. Increased pattern 7 is significantly associated with NK cells from patients responsive to anti-CTLA-4 or combined anti-CTLA-4 and anti-PD-1. Significant differences in mean pattern 7 weight between treatment groups are indicated by asterisks where p-values < 0.05 = *, < 0.01 = **, and < 0.001 = ***. B Box plot of projected pattern 7 weights across intratumoral NK cells from metastatic melanoma patients after treatment with ICI. Cells are colored by therapy and separated by patient response. Increased pattern 7 is associated with NK cells from patients responsive to combination anti-CTLA-4 + anti-PD-1. Significant differences in mean pattern 7 weight between treatment groups are indicated by asterisks where p-values < 0.05 = *, < 0.01 = **, and < 0.001 = ***. C ROC curve for the performance of pattern 7 weights in predicting response to anti-CTLA-4 prior to the administration of treatment. D Box plot of projected pattern 7 weights across flow-sorted intratumoral NK cells from metastatic melanoma tumors that were unresponsive ICI (intrinsic resistance) or developed acquired resistance after a period of initial response [6]. The dashed line indicates the average maximum value for pattern 7 across treatment groups. NK cells with elevated pattern 7 weights are seen in patients that had an initial response to ICI, with the highest observed weights from a patient that responded to anti-CTLA-4. E Box plot of projected pattern 7 weights across NK cells isolated from peripheral blood of metastatic melanoma patients that had no response to ICI (intrinsic resistance) or developed acquired resistance after a period of initial response. The dashed line indicates the average maximum value for pattern 7 from intratumoral NK cells across treatment groups. Elevated pattern 7 weights are not detected in circulating NK cells, regardless of response.

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