Immune Phenotype and Response to Neoadjuvant Therapy in Triple-Negative Breast Cancer.

Abstract

PURPOSE:

Increasing tumor-infiltrating lymphocytes (TIL) is associated with higher rates of pathologic complete response (pCR) to neoadjuvant therapy (NAT) in patients with triple-negative breast cancer (TNBC). However, the presence of TILs does not consistently predict pCR, therefore, the current study was undertaken to more fully characterize the immune cell response and its association with pCR.

EXPERIMENTAL DESIGN:

We obtained pretreatment core-needle biopsies from 105 patients with stage I-III TNBC enrolled in ARTEMIS (NCT02276443) who received NAT from Oct 22, 2015 through July 24, 2018. The tumor-immune microenvironment was comprehensively profiled by performing T-cell receptor (TCR) sequencing, programmed death-ligand 1 (PD-L1) IHC, multiplex immunofluorescence, and RNA sequencing on pretreatment tumor samples. The primary endpoint was pathologic response to NAT.

RESULTS:

The pCR rate was 40% (42/105). Higher TCR clonality (median = 0.2 vs. 0.1, P = 0.03), PD-L1 positivity (OR: 2.91, P = 0.020), higher CD3+:CD68+ ratio (median = 14.70 vs. 8.20, P = 0.0128), and closer spatial proximity of T cells to tumor cells (median = 19.26 vs. 21.94 μm, P = 0.0169) were associated with pCR. In a multivariable model, closer spatial proximity of T cells to tumor cells and PD-L1 expression enhanced prediction of pCR when considered in conjunction with clinical stage.

CONCLUSIONS:

In patients receiving NAT for TNBC, deep immune profiling through detailed phenotypic characterization and spatial analysis can improve prediction of pCR in patients receiving NAT for TNBC when considered with traditional clinical parameters.

• Authors: Clinton Yam, Er-Yen Yen, Jeffrey T Chang, Roland L Bassett, Gheath Alatrash, Haven Garber, Lei Huo, Fei Yang, Anne V Philips, Qing-Qing Ding, Bora Lim, Naoto T Ueno, Kasthuri Kannan, Xiangjie Sun, Baohua Sun, Edwin Roger Parra Cuentas, William Fraser Symmans, Jason B White, Elizabeth Ravenberg, Sahil Seth, Jennifer L Guerriero, Gaiane M Rauch, Senthil Damodaran, Jennifer K Litton, Jennifer A Wargo, Gabriel N Hortobagyi, Andrew Futreal, Ignacio I Wistuba, Ryan Sun, Stacy L Moulder, Elizabeth A Mittendorf
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 27 Issue 19 Pg. 5365-5375 (10 01 2021) ISSN: 1557-3265 [Electronic] United States
• PMID: 34253579 (Publication Type: Clinical Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: ©2021 American Association for Cancer Research.

Chemical References

• B7-H1 Antigen

Topics

• B7-H1 Antigen (genetics, metabolism)
• Humans
• Lymphocytes, Tumor-Infiltrating
• Neoadjuvant Therapy
• Phenotype
• Prognosis
• Triple Negative Breast Neoplasms (drug therapy, genetics)
• Tumor Microenvironment (genetics)