The progression of multiple primary lung cancer (MPLC) involves complex changes in cell composition and metabolic function. Here, we performed scRNA sequencing of 167,397 cells from six patients with MPLC, combined with bulk whole-exome sequencing. We revealed that both naïve and memory T cells participate in the differentiation of CD8+ T cells. The terminal states of CD8+ T cells are exhausted T cells, which respond to stimuli and positively regulate cell death, and cytotoxic T cells, which

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... mainly implicated in the regulation of cytokine production. Multiple functional Tregs and naïve T cells contribute to the origin of CD4+ T cells. B cells, with two main functions, also play important roles in the immune response. We also uncovered the cellular metabolic activities that occur during tumor invasion. Positive regulation of blood vessel diameter has been observed in endothelial cells, while angiogenesis has not been found in early glandular neoplasia of the lung. The development of epithelial cells involves two functional states. In one state, cells respond to stress from the immune system, and in the other, some will undergo programmed cell death or enter the cell cycle due to the selective pressure that arises over the course of tumor development in synchronous MPLC. Our study showed the complete landscape of different dynamic cellular changes, which might reveal the key cellular mechanisms of MPLC and therefore provide new clues for the pathogenesis of tumors.