Depletion of tumor cell–autonomous SHP2 reduces pulmonary metastasis, alters immune profiles, and prevents T-cell exhaustion. A, Schematic of the study using doxycycline-inducible depletion of SHP2 in 4T1 cells. Elements in the scheme were created using BioRender. BALB/c mice (n = 7 mice per group for shScramble and shPTPN11 146, n = 6 mice per group for shPTPN11 369) were orthotopically engrafted with 4T1 cells (5 × 104) via intraductal injection. Primary tumors were surgically removed 2 weeks following the injection. Doxycycline was administrated in drinking water at 2 mg/mL 3 days following the removal of primary tumors. B, Plots comparing the primary tumor volume at day 14 postinjection. NS, no significance. C, Representative bioluminescent images of 4T1 pulmonary metastasis at day 17 and day 31 postinjection. D, Bioluminescent values from pulmonary ROI quantified as the ratio of day 31 to day 17 postinjection (*, P < 0.05; **, P < 0.01).