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Enhanced humoral immunity in breast cancer patients with high serum concentration of anti-HER2 autoantibody.

ABSTRACT: Humoral immunity plays a substantial role in the suppression of breast cancer. We have revealed that a high serum concentration of anti-HER2 autoantibody (HER2-AAb) is associated with favorable outcomes in patients with invasive breast cancer. Thus, we aimed to clarify the association between high serum concentration of HER2-AAb and humoral immune response in the tumor microenvironment. Out of 500 consecutive patients with invasive breast cancer, we selected those whose HER2-AAb values were high (n = 33) or low (n = 20) based on the distribution of HER2-AAb values of 100 healthy individuals. Tumor and regional lymph node formalin-fixed paraffin-embedded samples prepared from the surgical specimens were subjected to immunohistochemistry. We confirmed that the recurrence-free survival of the high HER2-AAb group was significantly longer than that of the low HER2-AAb group (p = 0.015). The numbers of tumor-infiltrating CD20+ immune cells (ICs) (p < 0.001), IGKC+ICs (p = 0.023), and CXCL13+ ICs (p = 0.044) were significantly higher in the high HER2-AAb group than in the low HER2-AAb group. The number of CD4+ ICs in the B-cell follicles of the regional lymph nodes was also significantly greater in the high HER2-AAb group than in the low HER2-AAb group (p = 0.026). Our findings indicate that a high level of HER2-AAb is associated with enhanced humoral immunity against breast cancer and thus may provide a rationale for the association of HER2-AAb with favorable prognosis.

SUBMITTER: Sato Y

PROVIDER: S-EPMC7926031 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Enhanced humoral immunity in breast cancer patients with high serum concentration of anti-HER2 autoantibody.

Sato Yasufumi Y Shimoda Masafumi M Sota Yoshiaki Y Miyake Tomohiro T Tanei Tomonori T Kagara Naofumi N Naoi Yasuto Y Kim Seung Jin SJ Noguchi Shinzaburo S Shimazu Kenzo K

Cancer medicine 20210127 4

Humoral immunity plays a substantial role in the suppression of breast cancer. We have revealed that a high serum concentration of anti-HER2 autoantibody (HER2-AAb) is associated with favorable outcomes in patients with invasive breast cancer. Thus, we aimed to clarify the association between high serum concentration of HER2-AAb and humoral immune response in the tumor microenvironment. Out of 500 consecutive patients with invasive breast cancer, we selected those whose HER2-AAb values were high ...[more]

PMID: 33506656

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Project description:ObjectiveThis study aims to explore the relationship between serum calcium concentration and peripheral lymphocyte status/Th1/Th2 cytokine levels in SLE patients, and the effect of glucocorticoids (GCs) on the calcium concentration and immune cell activation.MethodsThe peripheral blood TBNK lymphocyte subsets and Th1/Th2 cytokines in SLE patients with low or normal serum calcium concentration and healthy people were analyzed and compared retrospectively. Peripheral white blood cells (PWBCs) from SLE patients or healthy people were stimulated with PMA or GCs in vitro to test their extracellular calcium concentration and CD8+ T cell activation.ResultsThe percentages of CD8+ T in SLE patients increased, but the increase of the number of CD8+ T cells only occurred in the SLE patients with low serum calcium concentration, and the number of CD45hiCD8+ T cells also increased, suggesting that SLE patients with hypocalcemia tend to possess an enhanced cellular immunity. The results of Th1/Th2 cytokines in peripheral blood showed that the levels of serum IL-2, IL-10, IL-6 and IFN-γ in SLE patients with hypocalcemia were significantly increased. Although the serum levels of TNF-α in SLE patients were -similar to that in healthy people, it was significantly higher than that in SLE patients with normal serum calcium. When comparing the results of Th1/Th2 cytokines in two times of one patient, the serum levels of TNF-α in SLE patients increased while serum calcium levels decreased. The in vitro experiments showed that the decrease of serum calcium concentration in SLE patients was affected by the immune cell activation and the application of GCs, but GCs did not promote the immune cell activation.ConclusionsLow serum calcium may make SLE patients in an enhanced cellular immune status and GCs aggravates the decrease of serum calcium levels but has no role on the immune cell activation. It suggests that hypocalcemia possibly promotes the disease activity of SLE patient, which should be paid attention to clinically.

Project description:PURPOSE:HER2 signaling functional activity may be important to measure in addition to HER2 protein quantification when identifying patients eligible for HER2 therapies. A HER2 Signaling Function (CELx HSF) Test for HER2-negative patients uses patient's live tumor cells on a biosensor to identify patients with abnormally high HER2-related signaling (HSFs+) likely to respond to anti-HER2 therapies. METHODS:The CELx HSF test was employed to: (1) characterize the sensitivity and specificity of the test to detect abnormal levels of HER2 signaling; (2) evaluate the inhibitory effectiveness of five different anti-HER2 therapies; (3) assess the correlation between CELx HSF test detection of abnormal HER2 signaling and response to HER2 therapy using xenograft models; and (4) confirm the prevalence of abnormal HER2 signaling amongst HER2-negative breast cancer patients (HER2-/HSFs+). RESULTS:HER2-/HSFs+?breast cancer patient samples were identified and showed sensitivity to five approved anti-HER2 therapies. Xenograft studies using both HER2+?and HER2- cell lines confirmed that CELx HER2 signaling status better predicts HER2 inhibitor efficacy than HER2 receptor status. In a study of 114 HER2-negative breast tumor patient samples, 27 (23.7%; 95% CI?=?17-32%) had abnormal HER2 signaling (HSFs+). A ROC curve constructed with this dataset projects the CELx HSF Test would have greater than 90% sensitivity and specificity to detect the HER2-/HSFs+?patient population. CONCLUSIONS:The CELx HSF test is a well-characterized functional biomarker assay capable of identifying dynamic HER2-driven signaling dysfunction in tumor cells from HER2-negative breast cancer patients. This test has demonstrated efficacy of various HER2 targeted therapies in live tumor cells from the HSFs+?population and correlated the test result to HER2 drug response in mouse xenograft studies. The proportion of HER2-negative breast cancer patients found to have abnormal HER2 signaling in a 114 patient sample study, 20-25%, is significant. A clinical trial to evaluate the efficacy of anti-HER2 therapies in this patient population is warranted.

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Enhanced humoral immunity in breast cancer patients with high serum concentration of anti-HER2 autoantibody.

Publications

Enhanced humoral immunity in breast cancer patients with high serum concentration of anti-HER2 autoantibody.

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