Thyroid cancer metastasis is associated with an overabundance of defective follicular helper T cells.

Metastatic thyroid cancers are more difficult to treat and have a significantly worse prognosis than localized thyroid cancers. Previous studies have shown that follicular helper T cells (Tfh) may participate in antitumor immune responses. Here, we investigated the characteristics of Tfh cells in patients with differentiated thyroid cancer (DTC) at various severities, including patients with localized disease, cervical metastasis, and distant metastasis. In circulating CD4 T cells, the proportion of CD4+ CXCR5+ Tfh-like cells was significantly higher in patients with distant metastasis than in healthy controls, patients with local disease, and patients with cervical metastasis. Also, the expression of Tfh cell-associated surface molecules, such as PD-1, ICOS, and BTLA, tended to be higher in patients with cervical and distant metastasis than in healthy controls. However, the expression of secreted molecules, such as IL-10, IL-21, and CXCL13, was significantly lower in patients with distant metastasis than in healthy controls and patients with local disease. Additionally, circulating Tfh-like cells from patients with distant metastasis were less capable of supporting B-cell growth and IgM secretion. We also examined the CD4+ CXCR5+ Tfh-like cells in tumor samples. Tumor-infiltrating Tfh-like cells were highly enriched in the pulmonary metastasis compared to the local tumor and the cervical metastasis. However, tumor-infiltrating Tfh-like cells from pulmonary metastasis displayed higher PD-1, TIM-3, and lower IL-21 expression than those from the local tumor. Together, this study identified that the metastasis of DTC patients was associated with an overabundance of defective Tfh cells.

Circulating CXCR5+CD4+ T cells assist in the survival and growth of primary diffuse large B cell lymphoma cells through interleukin 10 pathway.

Diffuse large B cell lymphoma (DLBCL) is a common and aggressive cancer caused by the malignant transformation of B cells. Although it has been established that the follicular helper T (Tfh) cells play a central role in B cell development, little information is available on their involvement in DLBCL pathogenesis. We studied the role of the peripheral Tfh equivalent, the CXCR5+ CD4+ T cells, in DLBCL. Data showed that compared to CXCR5- CD4+ T cells, CXCR5+ CD4+ T cells were significantly more effective at promoting the proliferation as well as inhibiting the apoptosis of primary autologous DLBCL tumor cells. Surprisingly, we found that at equal cell numbers, CXCR5+ CD4+ T cells in DLBCL patients secreted significantly less interleukin (IL)-21 than CXCR5- CD4+ T cells, while the level of IL-10 secretion was significant elevated in the CXCR5+ compartment compared to the CXCR5- compartment. Neutralization of IL-10 in the primary DLBCL-CXCR5+ CD4+ T cell coculture compromised the CXCR5+ CD4+ T cell-mediated pro-tumor effects, in a manner that was dependent on the concentration of anti-IL-10 antibodies. The CXCR5+ compartment also contained significantly lower frequencies of cytotoxic CD4+ T cells than the CXCR5- compartment. In conclusion, our investigations discovered a previously unknown pro-tumor role of CXCR5-expressing circulating CD4+ T cells, which assisted the survival and proliferation of primary DLBCL cells through IL-10.

Elevated B Cell Activation is Associated with Type 2 Diabetes Development in Obese Subjects.

BACKGROUND/AIMS: Despite strong association between obesity and the pathogenesis of type 2 diabetes (T2D), only a subset of obese individuals eventually develops T2D. We sought to determine the immunological factors behind this heterogeneity. METHODS: Peripheral blood of obese non-diabetic subjects and obese diabetic subjects were collected and the B cell responses in these subjects were analyzed. RESULTS: We found that the B cells from obese diabetic subjects had similar B cell subtype composition and secreted similar levels of low-grade pro-inflammatory cytokines to obese non-diabetic subjects, characteristic to the background chronic immune activation frequently observed in obese subjects. When examining adaptive B cell antibody responses, however, obese diabetic subjects presented much higher levels of polyclonal activation and antibody secretion, with impaired ability to response to new antigens such as seasonal influenza vaccination. CONCLUSIONS: These data demonstrated that in obese diabetic subjects, B cell adaptive response is impaired and potentially contribute to overall higher inflammation.

Changes of lipin1ß expression in gestational diabetes mellitus.

BACKGROUND: Lipin1ß is an adipokine proposed to be associated with insulin resistance (IR). Pregnancy is a physiologic state of progressive IR. The objective of the present study was to investigate the role of lipin1ß in the development of GDM. METHODS: A total of 40 pregnant women (22 normal and 18 with GDM) who delivered healthy infants at full-term (> 37 weeks gestation) were included. The mRNA and protein levels of lipin1ß in adipose tissues were determined by real-time RT-PCR and Western-blot. Plasma glucose, lipids, insulin, and estradiol (E2) levels were measured routinely at fasting state, and HOMA-IR was calculated accordingly. RESULTS: The lipin1ß expression in both mRNA and protein levels in SAT and VAT was lower in GDM patients than controls. Lipin1ß mRNA in VAT was negatively correlated with BMI (r = -0.505, p < 0.05), FINS (r = -0.539, p < 0.05), HOMA-IR (r = -0.574, p < 0.01), TG (r = -0.471, p < 0.05), and E2 (r = -0.564, p < 0.01). Lipin1ß mRNA expression in SAT was similar with VAT. Lipin1ß mRNA was not correlated with body weight gain or blood pressure. These results indicated that the lipin1ß expression in adipose tissues is down-regulated in patients with GDM. CONCLUSIONS: Lipin1ß might play a role in the pathogenesis of insulin resistance in GDM.