FIGURE 6 from Epithelial Expressed B7-H4 Drives Differential Immunotherapy Response in Murine and Human Breast Cancer

B7-H4 expression does not correlate with resistance to chemotherapy + immunotherapy in human breast tumors. Patients were from the I-SPY2 clinical trial (paclitaxel control and pembrolizumab arms) or the TBCRC 043 clinical trial (carboplatin control and atezolizumab arms). A, In breast tumors from the I-SPY2 clinical trial (control and pembrolizumab arms), B7-H4 expression is higher in TNBC tumors compared with HR+ tumors. Data were analyzed by unpaired t test. B, In the same patient cohort, B7-H4 expression is not higher in grade III tumors compared with grade I (orange dots) or II. Data analyzed by unpaired t test. C and D, B7-H4 expression is not correlated with pCR in tumors regardless of HR status, treated with either paclitaxel or paclitaxel + pembrolizumab (ICI). Data analyzed by unpaired t test. E, EFS in HR⁺ (n = 89) and TNBC (n = 62) tumors from the I-SPY2 cohort. Tumors with high B7-H4+ expression (top 33% of patients) have worse EFS when treated with paclitaxel alone and no survival benefit when treated with paclitaxel + ICI. Data were analyzed by log-rank Mantel–Cox test. F, In the metastatic setting, PFS stratified by B7-H4 expression (top and bottom 33% of cohort) from primary breast biopsy or metastatic lesion in patients from the TBCRC 043 trial does not correlate with B7-H4 expression in either control or carboplatin + atezolizumab (ICI) groups. Data were analyzed by log-rank Mantel–Cox test. G and H, We also assessed survival by treatment status. Metastatic tumors (H) from TBCRC 043 with high B7-H4 expression had significantly improved PFS to ICI, and nonmetastatic tumors (I-SPY2) had minimal improvement to ICI (G). Data were analyzed by log-rank Mantel–Cox test. n = 151 patients for A–E and G; n = 91 patients for F and H.