• IMMUNE NETWORK
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• v.20 no.6
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• pp.48.1-48.11
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• 2020

Hyperprogressive disease (HPD) is a distinct pattern of progression characterized by acceleration of tumor growth after treatment with anti-PD-1/PD-L1 Abs. However, the immunological characteristics have not been fully elucidated in patients with HPD. We prospectively recruited patients with metastatic non-small cell lung cancer treated with anti-PD-1/PD-L1 Abs between April 2015 and April 2018, and collected peripheral blood before treatment and 7-days post-treatment. HPD was defined as ≥2-fold increase in both tumor growth kinetics and tumor growth rate between pre-treatment and post-treatment. Peripheral blood mononuclear cells were analyzed by multi-color flow cytometry to phenotype the immune cells. Of 115 patients, 19 (16.5%) developed HPD, 52 experienced durable clinical benefit (DCB; partial response or stable disease ≥6 months), and 44 experienced non-hyperprogressive progression (NHPD). Patients with HPD had significantly lower progression-free survival (p<0.001) and overall survival (p<0.001). When peripheral blood immune cells were examined, the pre-treatment frequency of CD39⁺ cells among CD8⁺ T cells was significantly higher in patients with HPD compared to those with NHPD, although it showed borderline significance to predict HPD. Other parameters regarding regulatory T cells or myeloid derived suppressor cells did not significantly differ among patient groups. Our findings suggest high pre-treatment frequency of CD39⁺CD8⁺ T cells might be a characteristic of HPD. Further investigations in a larger cohort are needed to confirm our results and better delineate the immune landscape of HPD.

• Asian-Australasian Journal of Animal Sciences
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• v.24 no.5
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• pp.696-706
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• 2011

The objective of this study was to characterize serum immunoglobulins and lymphocytes subpopulations in the peripheral blood mononuclear cells (PBMCs) of Holstein calves in response to lipopolysaccharide (LPS) challenge from Escherichia coli. Fourteen calves received subcutaneous injections of E. coli LPS at 10 weeks of age, and six calves were injected with saline as a control. The concentrations of total serum IgG and the relative amount of LPS-specific IgG in calves challenged with LPS were significantly higher (p<0.05) compared to control animals and LPS challenge significantly increased (p<0.05) the percentage of $CD5^+$ and $CD21^+$ T cells in PBMCs. Meanwhile, LPS challenge significantly increased (p<0.05, p<0.01) the percentage of $CD8^+$ and $CD25^+$ T cells in peripheral blood mononuclear cells (PBMC) at 7 and 14 Day-post LPS challenge (DPLC), respectively. The composition of $CD4^+CD25^+$ T cells and $CD8^+CD25^+$ T cells from calves challenged with LPS was also higher (p<0.05 and p = 0.562, respectively) than those of control calves at 14 DPLC. In conclusion, LPS challenge not only induces production of IgG with expression of B-cell immune response related cell surface molecules, but also stimulates activation of T-lymphocytes in PBMC. Our results suggest that LPS challenge in calves is a good model to elucidate cellular immune response against Gram-negative bacterial infections.

• Environmental Analysis Health and Toxicology
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• v.3 no.1_2
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• pp.9-19
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• 1988

The effect of rancid perilla oil on the immune response in mice was studied. ICR male mice were divided into 5 groups and were fed on the experimental diets for 4 weeks. Mice were sensitized and challenged with sheep red blood cell. Immune responses were evaluated by antibody production, Arthus reaction, delayed type hypersensitivity (DTH), Rosette forming cell and macrophage activity. Biochemical items were measured by serum protein and serum albumin. The weight of spleen, thymus and liver were measured. The rancid perilla oil diets decreased humoral and cellular immune responses, the number of peripheral circulating white blood cells and total protein and serum albumin. These results showed that the high rancid perilla oil diet decreased more humoral and cellular immune response, the number of peripheral circulating white blood cells, and total protein and serum albumin than the low rancid perilla oil diet did.

• Clinical and Experimental Reproductive Medicine
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• v.16 no.2
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• pp.147-152
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• 1989

The purpose of this study is to detect certain change in peripheral blood lymphocyte subpopulations in women with premature ovarian failure. The B cells, T cells and subsets were counted in 21 women with premature ovarian failure and 30 age-matched normal control women. The B cells were measured by identifying lymphocyte with surface membrane immunoglobulin and T cells and subsets by indirect immunofluorescence technique with the monoclonal antibodies OK T3, OK T4, and OK T8. The results were as follows. 1. No significant difference in the absolute number of B cells, T cells and subsets between women with premature ovarian failure and normal control women was observed. 2. The percentage of B cells, T cells and OK T8(+) cells in women with premature ovarian failure was not significantly different from that in normal control subjects respectively. 3. The percentage of OK T4(+) cells and OK T4/0K T8(+) ratio was significantly higher in women with premature ovarian failure than in control subjects.

• IMMUNE NETWORK
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• v.16 no.2
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• pp.126-133
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• 2016

Unlike conventional T cells, innate CD8 T cells develop a memory-like phenotype in the thymus and immediately respond upon antigen stimulation, similar to memory T cells. The development of innate CD8 T cells in the thymus is known to require IL-4, which upregulates Eomesodermin (Eomes). These features are similar to that of virtual memory CD8 T cells and IL-4-induced memory-like CD8 T cells generated in the peripheral tissues. However, the relationship between these cell types has not been clearly documented. In the present study, IL-4-induced memory-like CD8 T cells generated in the peripheral tissues were compared with innate CD8 T cells in terms of phenotype and function. When an IL-4/anti-IL-4 antibody complex (IL-4C) was injected into C57BL/6 mice daily for 7 days, the Eomes^hiCXCR3⁺ CD8 T cell population was markedly increased in the peripheral lymphoid organs and blood. These cells were generated from naïve CD8 T cells or accumulated via the expansion of pre-existing CD44^hiCXCR3⁺ CD8 T cells. Initially, the majority of these CXCR3⁺ CD8 T cells expressed low levels of CD44, which was followed by the conversion to the CD44^hi phenotype. This conversion was associated with the acquisition of enhanced effector function. After discontinuation of IL-4C treatment, Eomes expression levels gradually decreased in CXCR3⁺ CD8 T cells. Taken together, the results of this study demonstrate that IL-4-induced memory-like CD8 T cells generated in the peripheral lymphoid tissues are phenotypically and functionally similar to the innate CD8 T cells generated in the thymus.

• Journal of Gastric Cancer
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• v.3 no.4
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• pp.201-205
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• 2003

Purpose: Telomerase activity is generally absent in primary cell cultures and normal tissues. Telomerase is known to be induced upon immortalization or malignant transformation of human cells. Telomerase activity can be increased in immature lymphocytes and activated lymphocytes, but it is not detected in the peripheral blood of normal persons. The authors analyzed peripheral blood telomerase from patients of gastric cancer to evaluate the possibility of using it for diagnosis and as a prognostic factor. Materials and Methods: We obtained blood samples from 11 inflammatory patients and 64 gastric cancer patients. The telomerase activity was measured using the [PCR-ELISA] method. The results were correlated with the T, N, M stage, cell differentiation, vascular, neural, and lymphatic invasion, tumor size, and tumor location. Results: In the 11 inflammatory patients, telomerase activity was not detected while in the gastric cancer patients, a positive rate of $28.1\%$ was noted. The peripheral telomerase activity was not related with tumor size, tumor site, lymphatic and vascular invasion, stage, or histologic differentiation. Conclusion: The peripheral blood telomerase activity for patients of gastric cancer can be utilized as a marker for the diagnosis of not only advanced gastric cancer, but also relatively early stage gastric cancer, but not as a prognostic factor.

• Restorative Dentistry and Endodontics
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• v.25 no.4
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• pp.606-618
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• 2000

Dental pulp infection is most commonly caused by extensive dental caries, and some bacterial species invade root canals; bacterial components and products are thought to be associated with the pathogenesis of periapical periodontitis. A principle driving force behind pulpal disease response appears to lie in the host immune system's to bacteria and their products. We examined the production of interleukin $1{\beta}$ (IL-$1{\beta}$) and tumor necrosis factor ${\alpha}$(TNF-${\alpha}$) from human peripheral mononuclear cells, lymphocytes and monocytes stimulated by heat-killed Acitnobacillus actinomycetemcomitans (ATCC 29523), Porphyromonas gingivalis (ATCC 33277) and Prevotella intermedia (ATCC 25611), and also by their sonicated bacterial extracts (SBE), respectively. The effects of three strains of heat-killed bacteria and their SBEs on the morphology of cultured blood cell lines HL-60 (KCLB 10240) and J774A.1 (KCLB 40067) were observed under the inverted microscope. Ultrastructural changes of J774A.1 exposed to heat-killed P. intermedia and its SBE were investigated using transmission electron microscopy. Production of IL-$1{\beta}$ was reduced in human peripheral mononuclear cells after stimulation by sonic bacterial extracts of A. actinomycetemcomitans, P. gingivalis, and P. intermedia. Heat-killed and sonic extract of P. gingivalis inhibited the production of TNF-${\alpha}$ in peripheral mononuclear cells. Production of TNF-${\alpha}$ was inhibited in peripheral monocytes after stimulation by sonic extracts of A. actinomycetemcomitans, P. gingivalis, and P. intermedia. HL-60 and J 774A.1 cells showed granular degeneration after treatment with heat-killed and sonic extracts of A. actinomycetemcomitans, P. gingivalis, and P. intermedia Chromatin margination and shrinkage were observed in 774A.1 treated with heat-killed P. intermedia. Cell wall structure and organelles were destroyed and vacuoles were formed in cytoplasm in J774A.1 treated with P. intermedia sonic extract. These results suggest that A actinomycetemcomitans, P gingivalis and P intermedia may have an important role in the formation and progression of pulpal diseases via both modulation of production of IL-$1{\beta}$ and TNF-${\alpha}$ from blood mononuclear cells and cytopathic effects.

• Journal of Digestive Cancer Research
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• v.11 no.1
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• pp.21-29
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• 2023

Despite recent advancements in the diagnosis and treatment of pancreatic cancer, clinical results remain dismal. Furthermore, there are no reliable biomarkers or alternatives beyond carbohydrate antigen 19-9. Circulating tumor cells (CTCs) may be a potential biomarker, but their therapeutic application is constrained by their rarity in peripheral venous blood. Theoretically, the portal vein can be a more appropriate location for the detection of CTCs, because the first venous drainage of pancreatic cancer is portal circulation. According to several studies, the number and detection rate of CTCs may be higher in the portal blood than in the peripheral blood. CTC counts in the portal blood are strongly correlated with several prognostic parameters such as hepatic metastasis, recurrence after surgery, and survival. The phenotypic and genotypic properties analyzed in the captured portal CTCs can assist us to comprehend tumor heterogeneity and predicting the prognosis of pancreatic cancer. The investigations to date are limited by small sample sizes and varied CTC detection techniques. Therefore, a large number of prospective studies are required to confirm portal CTCs as a valid biomarker in pancreatic cancer.

• Proceedings of the Korean Nuclear Society Conference
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• 2002.05a
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• pp.388-388
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• 2002

• Journal of Animal Science and Technology
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• v.53 no.6
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• pp.563-569
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• 2011

The effects of cortisol on proliferation and apoptosis of tilapia surface immunoglobulin positive ($sIg^+$) lymphocytes isolated from different tissues were investigated. $sIg^+$ lymphocytes from the tilapia head kidney (HK) and spleen showed a higher proliferation and lower intracellular calcium ($Ca^{2+}{_i}$) level to Ig-crosslinking compared with peripheral blood $sIg^+$ lymphocytes. Peripheral blood $sIg^+$ lymphocytes stimulated with lipopolysaccharide (LPS) showed high levels of apoptosis in the presence of cortisol. HK and to a lesser extent spleen $sIg^+$ lymphocytes, although less sensitive than their equivalent in peripheral blood, showed cortisol-induced apoptosis irrespective of LPS stimulation of control levels. Compared to plasma values measured during stress conditions, proliferation regardless of LPS stimulation was apparently suppressed by cortisol that is effective in inducing a significant increase in apoptosis in all three different cell populations of $sIg^+$ cells, suggesting the immunoregulatory effect of cortisol in both LPS stimulated and non-stimulated conditions. Different sensitivity of $sIg^+$ cells to the cortisol, in regard to developmental stage and activity, could be related in inhibiting excessive and continuing depletion of $sIg^+$ lymphocytes.