Perivascular macrophages restrict CXCR4-dependent accumulation of stem-like CD8(+) T cells in tumors and limit chemotherapy efficacy.

HO-1 activity in LYVE-1+ perivascular tumor-associated macrophages restricts CXCR4-dependent accumulation of stem-like CD8+ T cells in murine breast tumors, limiting chemotherapy efficacy.

• Why it matters: The perivascular niche shapes immune-stromal crosstalk during chemotherapy, but how PvTAM function regulates stem-like CD8+ T cell buildup and treatment response is unclear.
• What they did: In murine breast cancer models, the authors tracked the tumor microenvironment after HO-1 inhibition or genetic inactivation in LYVE-1+ PvTAMs and cytotoxic chemotherapy, then tested CXCR4 dependence and stromal links to CXCL12+ CD34+ Pv CAFs.
• The result: Stem-like TCF1+ PD-1+ CD8+ T cells increased during transition to immunological control, and their tumor accumulation depended on CXCR4 and correlated with treatment-induced expansion of CXCL12+ CD34+ Pv CAFs; in human breast cancer, a higher stem-like CD8+ T cell program was associated with improved outcomes after CCT.

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