<i>In vivo</i> and morphological experiments demonstrated that CYP27A1<sup>+</sup>TAMs effectively suppressed tumor growth and increased CD8<sup>+</sup>T cells infiltration in the TIME.<h4>Conclusion</h4>This study highlights the importance of spatial niches in understanding the TIME of NSCLC and predicting ICB responses. The gene discussed is CYP27A1; the disease is neoplasm.