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By leveraging deep molecular profiling through spatial transcriptomics integrated with single-cell RNA-sequencing from public atlases, and serum proteomic profiling, we report a case of a patient with resectable NSCLC and a solitary synchronous brain metastasis showing a complete pathologic response after chemo-immunotherapy, and a durable event-free survival. The deep profiling of the tumor immune microenvironment of both pre-treatment brain metastasis and post-treatment primary lung tumor tissues unveiled a key role of B lymphocytes at different maturation state, spanning from na\u00efve to plasma cells, in mediating tumor eradication. Notably, the formation of several tertiary lymphoid structures in the regression bed of post-treatment primary tumor was observed, suggesting the in situ generation of high-affinity antibody and specific immune memory response. 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