TY - JOUR
T1 - Immune phenotype and response to neoadjuvant therapy in triple-negative breast cancer
AU - Yam, Clinton
AU - Yen, Er Yen
AU - Chang, Jeffrey T.
AU - Bassett, Roland L.
AU - Alatrash, Gheath
AU - Garber, Haven
AU - Huo, Lei
AU - Yang, Fei
AU - Philips, Anne V.
AU - Ding, Qing Qing
AU - Lim, Bora
AU - Ueno, Naoto T.
AU - Kannan, Kasthuri
AU - Sun, Xiangjie
AU - Sun, Baohua
AU - Cuentas, Edwin Roger Parra
AU - Symmans, William Fraser
AU - White, Jason B.
AU - Ravenberg, Elizabeth
AU - Seth, Sahil
AU - Guerriero, Jennifer L.
AU - Rauch, Gaiane M.
AU - Damodaran, Senthil
AU - Litton, Jennifer K.
AU - Wargo, Jennifer A.
AU - Hortobagyi, Gabriel N.
AU - Futreal, Andrew
AU - Wistuba, Ignacio I.
AU - Sun, Ryan
AU - Moulder, Stacy L.
AU - Mittendorf, Elizabeth A.
N1 - Publisher Copyright:
2021 American Association for Cancer Research
PY - 2021/10/1
Y1 - 2021/10/1
N2 - 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 ¼ 0.2 vs. 0.1, P ¼ 0.03), PD-L1 positivity (OR: 2.91, P ¼ 0.020), higher CD3þ:CD68þ ratio (median ¼ 14.70 vs. 8.20, P ¼ 0.0128), and closer spatial proximity of T cells to tumor cells (median ¼ 19.26 vs. 21.94 mm, P ¼ 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.
AB - 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 ¼ 0.2 vs. 0.1, P ¼ 0.03), PD-L1 positivity (OR: 2.91, P ¼ 0.020), higher CD3þ:CD68þ ratio (median ¼ 14.70 vs. 8.20, P ¼ 0.0128), and closer spatial proximity of T cells to tumor cells (median ¼ 19.26 vs. 21.94 mm, P ¼ 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.
UR - http://www.scopus.com/inward/record.url?scp=85117833352&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85117833352&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-21-0144
DO - 10.1158/1078-0432.CCR-21-0144
M3 - Article
C2 - 34253579
AN - SCOPUS:85117833352
SN - 1078-0432
VL - 27
SP - 5365
EP - 5375
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 19
ER -