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Immune correlates of the differing pathological and therapeutic effects of neoadjuvant chemotherapy in breast cancer.
Kim, Ryungsa; Kawai, Ami; Wakisaka, Megumi; Sawada, Sayaka; Shimoyama, Mika; Yasuda, Naomi; Hidaka, Masayuki; Morita, Yukitaka; Ohtani, Shoichiro; Arihiro, Koji.
Afiliação
  • Kim R; Breast Surgery, Hiroshima Mark Clinic, Hiroshima, Japan. Electronic address: ryu@hbc-center.com.
  • Kawai A; Breast Surgery, Hiroshima Mark Clinic, Hiroshima, Japan.
  • Wakisaka M; Breast Surgery, Hiroshima Mark Clinic, Hiroshima, Japan.
  • Sawada S; Breast Surgery, Hiroshima Mark Clinic, Hiroshima, Japan.
  • Shimoyama M; Breast Surgery, Hiroshima Mark Clinic, Hiroshima, Japan.
  • Yasuda N; Breast Surgery, Hiroshima Mark Clinic, Hiroshima, Japan.
  • Hidaka M; Genetic Testing Gene Research, Hiroshima, Japan.
  • Morita Y; Genetic Testing Gene Research, Hiroshima, Japan.
  • Ohtani S; Department of Breast Surgery, Hiroshima City Hospital, Hiroshima, Japan.
  • Arihiro K; Department of Anatomical Pathology, Hiroshima University Hospital, Hiroshima, Japan.
Eur J Surg Oncol ; 46(1): 77-84, 2020 01.
Article em En | MEDLINE | ID: mdl-31563296
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Quimioterapia Adjuvante / Microambiente Tumoral Limite: Adult / Aged / Female / Humans / Middle aged Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Quimioterapia Adjuvante / Microambiente Tumoral Limite: Adult / Aged / Female / Humans / Middle aged Idioma: En Ano de publicação: 2020 Tipo de documento: Article