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

Lauren E. McLemore, Murali Janakiram, Joseph Albanese, Nella Shapiro, Yungtai Lo, Xingxing Zang, Susan Fineberg

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)611-619
Number of pages9
JournalApplied Immunohistochemistry and Molecular Morphology
Volume26
Issue number9
DOIs
StatePublished - Oct 1 2018

Keywords

  • CD68
  • PD-L1
  • breast cancer
  • neoadjuvant chemotherapy
  • tumor-infiltrating lymphocytes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology
  • Medical Laboratory Technology

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