Significance of systemic and local immune responses to the pathological therapeutic effect of neoadjuvant chemotherapy in breast cancer
| العنوان: | Significance of systemic and local immune responses to the pathological therapeutic effect of neoadjuvant chemotherapy in breast cancer |
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| المؤلفون: | Shoichiro Ohtani, Yukitaka Morita, Ami Kawai, Ryungsa Kim, Koji Arihiro, Masayuki Hidaka, Mika Shimoyama, Naomi Yasuda, Sayaka Sawada, Yuri Funaoka, Megumi Wakisaka |
| المصدر: | Journal of Clinical Oncology. 37:e12084-e12084 |
| بيانات النشر: | American Society of Clinical Oncology (ASCO), 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Cancer Research, Tumor microenvironment, Chemotherapy, business.industry, medicine.medical_treatment, Therapeutic effect, medicine.disease, Breast cancer, Immune system, Oncology, medicine, Cancer research, business, Pathological |
| الوصف: | e12084 Background: Activation of the immune response including T lymphocytes, natural killer (NK) cells, and tumor microenvironment factors (TMEFs) is important in inducing a therapeutic response after neoadjuvant chemotherapy (NAC) in breast cancer. We examined the significance of systemic and local immune responses to the pathological therapeutic effect of NAC in breast cancer. Methods: From 2012 to 2018, 38 patients with stage II–III breast cancer received NAC with anthracyclines and taxanes followed by surgery. Therapeutic effects were evaluated according to the histopathology criteria for the assessment of therapeutic effects in breast cancer indicated by the Japanese Breast Cancer Society. Peripheral NK (pNK) cell activity was measured by chromium release assay. Levels of TMEFs were assessed by next-generation sequencing for CD4, CD8, NK, FOXP3, CTLA-4, PD-1, PD-L1, IL-2, IL-6, IL-12, IFN-γ, IL-10, TGF-β, and VEGF in FFPE sections collected from preoperative VAB samples and surgical specimens. Results: The stages, tumor subtypes, and therapeutic outcomes were as follows: II (N = 21), III (N = 17); luminal (N = 22), HER-2 positive (N = 12), TN (N = 4); G1a (N = 8), G1b (N = 13), G2a (N = 7), G2b (N = 4), G3 (i.e. complete) (N = 6). A G2 or better therapeutic effect were significantly associated with high post-NAC levels of NK, and potentially associated with higher CD4, CD8, and lower CTLA-4 after NAC. Multivariate logistic regression analysis showed that a G2 or better therapeutic effect was significantly associated with higher NK after NAC (OR = 1.07; 95% CI, 1.00–1.14; P = .0255). Disappearance of axillary lymph node metastasis was significantly associated with increased NK and pNK cell activity, as well as decreased VEGF level, and potentially associated with lower CTLA-4 after NAC. Conclusions: Increased NK cells after NAC are critical in producing a better therapeutic effect in collaboration with increased CD4 and CD8, and decreased CTLA-4 and VEGF. Systemic activation of pNK cells may improve the elimination of metastatic tumor cells in axillary lymph nodes by coordinating with release of immunosuppression derived from VEGF and activation of immune cells in the tumor microenvironment in breast cancer patients after NAC. An immune checkpoint inhibitor targeting CTLA-4 may improve NAC efficacy for breast cancer. |
| تدمد: | 1527-7755 0732-183X |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::a148010adb3683a35f6ed179351362da https://doi.org/10.1200/jco.2019.37.15_suppl.e12084 |
| رقم الأكسشن: | edsair.doi...........a148010adb3683a35f6ed179351362da |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15277755 0732183X |
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