WCLC 2025 - Posters & ePosters-EP.08.43 Surgical Stress After Lung Cancer Surgery Triggers the Outgrowth of Distant Metastases

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This study from Shiga University of Medical Science, Japan, investigates how surgical stress after lung cancer surgery influences the development of distant metastases. Even in early-stage lung cancer, circulating tumor cells (CTCs) enter the bloodstream and can become dormant in distant tissues. Typically, the immune system clears most CTCs, but some survive and may later grow by recruiting immunosuppressive cells. Surgical stress is suggested to increase these immunosuppressive cells, contributing to tumor recurrence, although the exact immune cell types involved had not been fully identified.<br /><br />The researchers aimed to pinpoint which immunosuppressive cells trigger metastasis growth post-surgery and to track their dynamics. They found that elevated postoperative blood monocytes correlate with higher recurrence rates in patients. Using a lung cancer mouse model, the study demonstrated that surgery increases monocyte levels in the blood and promotes lung metastases. Monocytes, derived from bone marrow and characterized as Ly6c-positive cells, are recruited to metastatic lung lesions after surgery and then differentiate into macrophages (marked by CD206 expression).<br /><br />Importantly, the chemokine MCP-1 was identified as a key factor recruiting monocytes to metastatic sites and aiding their differentiation into tumor-associated macrophages, which support tumor growth. Treatment with an MCP-1 inhibitor effectively reduced monocyte and macrophage presence in metastatic lesions and significantly suppressed lung cancer metastases post-surgery.<br /><br />In conclusion, surgical stress alters the immune environment both systemically and locally, facilitating tumor progression by recruiting monocytes that become tumor-promoting macrophages. Targeting this pathway with MCP-1 inhibitors offers a promising strategy for perioperative immune modulation to prevent postoperative lung cancer relapse. This research emphasizes the critical role of immune cell dynamics in cancer metastasis and suggests new avenues for therapeutic intervention after lung cancer surgery.

Asset Subtitle

Yo Kawaguchi

Meta Tag

Speaker Yo Kawaguchi

Topic Local-Regional Non-small Cell Lung Cancer

Keywords

lung cancer

surgical stress

distant metastases

circulating tumor cells (CTCs)

immunosuppressive cells

monocytes

macrophages

MCP-1 chemokine

tumor-associated macrophages

perioperative immune modulation