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An Immunoscore Using PD-L1, CD68, and Tumor-infiltrating Lymphocytes (TILs) to Predict Response to Neoadjuvant Chemotherapy in Invasive Breast Cancer

McLemore, Lauren E., DO, MPH*; Janakiram, Murali, MD; Albanese, Joseph, MD, PhD*; Shapiro, Nella, MD; Lo, Yungtai, PhD*,§; Zang, Xingxing, PhD†,∥; Fineberg, Susan, MD*

Applied Immunohistochemistry & Molecular Morphology: October 2018 - Volume 26 - Issue 9 - p 611–619
doi: 10.1097/PAI.0000000000000485
Research Articles

Response to neoadjuvant chemotherapy (NAC) in invasive breast cancer (IBC) is partly regulated by the immune microenvironment. We evaluated immune checkpoint PD-L1 expression, presence of CD68+ cells of macrophage/monocytic lineage and stromal tumor-infiltrating lymphocytes (TILs) in prechemotherapy biopsies and correlated with NAC response. We studied 76 cases of IBC. Prechemotherapy biopsies with >30% TILs were considered lymphocyte-rich IBC. We performed immunohistochemistry for PD-L1 and CD68. Prechemotherapy cores showing >1% PD-L1+ immune or tumor cells were considered positive. CD68 was positive if >40% of tumor stroma contained CD68+ cells or atleast 50% of tumor cells showed infiltration by CD68+ cells. Residual Cancer burden (RCB) Score of 0/I represented excellent response to NAC and RCB II or III unfavorable response. Thirty-five patients had RCB 0/I and 41 pts RCB II/ III. TILs>30% were present in prechemotherapy biopsies in 19 pts of whom 14 showed RCB 0/I (P=0.0075). Twenty-seven cases were PD-L1+ and 20 had an RCB 0/I (P=0.0003). Twenty-two cases were CD68+ of whom 18 showed RCB 0/I (P=<0.0001) There was a significant association between TILs>30%, PD-L1+ and CD68+ expression. Using atleast one of these immunologic parameters identified 26 of 35 patients with RCB 0/I and showed a higher sensitivity for response prediction than TILs alone (40% vs. 74.3%). In conclusion we demonstrate that high numbers of CD68+ monocytic/macrophage cells and PD-L1 expression in IBC shows significant association with NAC response. An immune biomarker profile including TILs, PD-LI and CD68 is more sensitive for NAC response prediction than TILs alone.

Departments of *Pathology


§Epidemiology and Population Health, Montefiore Medical Center and the Albert Einstein College of Medicine

Department of Surgery, Eastchester Center for Cancer Care and Montefiore Medical Center

Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY

The authors declare no conflict of interest.

Reprints: Susan Fineberg, MD, Department of Pathology, Montefiore Medical Center, 4th floor silver Zone, 111 East 210th Street, Bronx, NY 10467 (e-mail:

Received July 31, 2016

Accepted November 6, 2016

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