Deciphering the Immunomodulatory Function of GSN <sup>+</sup> Inflammatory Cancer-Associated Fibroblasts in Renal Cell Carcinoma Immunotherapy: Insights From Pan-Cancer Single-Cell Landscape and Spatial Transcriptomics Analysis.

NF kappa B signalling pathway showed a decreasing trend in ICI responders, while displaying an unstable trend in ICI non‐responders (Figure 5D , Figure S6A ), indicating the possible activation of NF kappa B signalling pathway in Tem/Teffe cells of responders.

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Besides, the activities of STING signalling pathway (Figure 5I , Figure S6B ), NOTCH signalling pathway (Figure 5N , Figure S6C ) and IL6_JAK_STAT3 signalling pathway (Figure 5S , Figure S6D ) were unstable in responders, while their activities showed a slightly increasing trend in non‐responders, demonstrating the probable activations of these signalling pathways in CD8 + Tex of non‐responders.

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Utilising 113 predictive ML combinations and LOOCV framework, we refined a highly significant model and benchmarked it against previously established ICI‐related signatures (Figure 2A ).

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