Immune correlates of the differing pathological and therapeutic effects of neoadjuvant chemotherapy in breast cancer. Issue 1 (January 2020)

• Record Type: Journal Article
• Authors: Kim, Ryungsa; Kawai, Ami; Wakisaka, Megumi; Sawada, Sayaka; Shimoyama, Mika; Yasuda, Naomi; Hidaka, Masayuki; Morita, Yukitaka; Ohtani, Shoichiro; Arihiro, Koji
• Is Part Of: European journal of surgical oncology. Volume 46:Issue 1(2020)
• Page Start: 77
• Page End: 84
• Publication Date: 2020-01
• Subjects: Breast cancer -- Neoadjuvant chemotherapy -- Pathological and therapeutic effects -- Immune response -- Tumor microenvironment; Oncology -- Periodicals; Cancer -- Surgery -- Periodicals; Medical Oncology -- Periodicals; Neoplasms -- surgery -- Periodicals; Cancer -- Chirurgie -- Périodiques; Cancérologie -- Périodiques; Oncologie; Chirurgie (geneeskunde); Electronic journals; Electronic journals -- Sciences; Electronic journals -- Medicine; Electronic journals; 616.994059005
• DOI: 10.1016/j.ejso.2019.09.146
• Languages: English
• ISSNs: 0748-7983

Abstract

Abstract: Purpose: To evaluate immune responses paralleling the pathological and therapeutic effects of neoadjuvant chemotherapy (NAC) in the tumor microenvironment of breast cancer. Patients and Methods: 38 patients with stages II and III breast cancer received NAC followed by surgery in 2012–2018. Peripheral natural killer (pNK) cell activity, tumor-infiltrating lymphocytes (TILs), and levels of tumor microenvironmental factors were assessed before and after NAC. Results: In univariate analysis, grade 2 (G2) and better therapeutic effects were significantly associated with high post-NAC levels of NK cells and interleukin-6, and tended to be associated with higher CD4, CD8 and CTLA-4 transcripts. Disappearance of axillary lymph node metastasis (Ax+) was significantly associated with 1) increased NK and pNK levels, 2) decreased vascular endothelial growth factor (VEGF) transcripts after NAC, 3) the presence of ≥5% TILs, and tended to be associated with higher CTLA-4 levels before NAC. Multivariate analysis showed that G2 and better therapeutic effects were significantly associated with higher NK levels after NAC (OR = 1.07, 95% CI 1.00–1.14; p = 0.0255), and that disappearance of Ax+ was significantly associated with the presence of ≥5% pre-NAC TILs (OR = 19.87, 95% CI 2.24–175.80; p = 0.0072). Conclusions: Increased NK cells after NAC, together with increased CD4 + and CD8 + T-cells, and decreased CTLA-4+ T cells and VEGF correlate with beneficial therapeutic effects. Systemic activation of pNK cell activity and the presence of pre-NAC TILs may improve the elimination of Ax + together with decreased immunosuppression by VEGF in tumors.