In this study, we aim to investigate the correlation between circulating tumor cells (CTCs) and the T lymphocyte subsets and NK cells in peripheral blood in non-small-cell lung cancer (NSCLC). The peripheral blood CTCs were determined by SET-iFISH. Flow cytometry was used to determine the distribution of T lymphocyte subsets and NK cells. Forty-one (49%) patients showed positivity for CTCs. Logistic regression analysis revealed CTC number was negatively correlated with the ratio of CD3+, CD4+, CD4+/CD8+, and NK % in patients at stage IV, while in a positive correlation was noticed between CTC number and regulatory T cell (Tregs) ratio in these patients. Multivariate analysis was performed in combination with the clinical-pathological materials to identify the risk factors for CTC positivity. Differentiation, NSCLC stage, percentages of CD3+CD4+ cells, Tregs, and NK cells were the independent risk factors for CTCs. CTCs were associated with the decrease of immune surveillance in the peripheral blood in NSCLC patients. The decrease of immune surveillance contributed to the escape of CTCs from the killing effects of the immunocytes, as well as the formation of metastasized lesions in the target organs.

/pdf/circulating-tumor-cells-were-associated-with-the-number-of-t-51eco85s4i.pdf

Circulating Tumor Cells Were Associated with the Number of T Lymphocyte Subsets and NK Cells in Peripheral Blood in Advanced Non-Small-Cell Lung Cancer.

In this study, we introduce a new model for vascularized skin and bone marrow transplantation. Twenty-five Lewis (RT11) rats were studied. Anatomic dissection studies were performed in 5 animals. In the experimental group, 10 isograft transplantations were performed between Lewis rats. Combined groin skin and femoral bone flaps were transplanted based on the femoral artery and vein. Transplants were evaluated on a daily basis. All flaps survived without problems over 100 days posttransplant. The skin component remained pink and pliable, and grew new hair. Histological examination of the femoral bone (except the femoral head) revealed active hematopoiesis with a viable compact and cancellous bone components on day 100 posttransplant. This model can be applied to tolerance induction studies across the major Histocompatibility (MHC) barrier, where bone will serve as donor of stem and progenitor cells, and the skin flap will serve as a monitor of graft rejection. © 2004 Wiley-Liss, Inc.

Composite vascularized skin/bone graft model: a viable source for vascularized bone marrow transplantation.

In 1970, Gershon was the first to propose that T cells, in addition to their helper activity, can also play a role as regulatory cells capable of suppressing immune responses. However, the initial strong interest in T cell-mediated suppression was followed by a period of doubt and skepticism. Since the late 1990s the “S” word started to be used in immunology again and interest in T suppressor cells has grown, ushering in a new renaissance for the field. In this article the author presents the current knowledge about a new subject called “skin-induced tolerance”? Suppression is induced via epicutaneous immunization and is described in both Th1- and Tc1-mediated contact sensitivity reactions. The subject of skin-induced tolerance is also considered in the regulation of experimental models of autoimmune diseases such as allergic autoimmune encephalomyelitis and collagen-induced arthritis and finally in an animal model of graft rejection. The last part of this presentation will introduce the very fresh subject of “contrasuppression”? or the reversal of skin-induced suppression.

Skin-induced tolerance and its reversal by Toll-like receptor ligands.

http://if-pan.krakow.pl/pjp/pdf/2006/3_439.pdf

Effect of ovoalbumin on the survival of an H-Y incompatible skin graft in C57BL/6 mice.

http://www.if-pan.krakow.pl/pjp/pdf/2014/2_192_ab.pdf

Skin-induced tolerance as a new needle free therapeutic strategy

Immune events developing in the bed of skin allograft and draining lymphatics and lymph nodes are probably a copy of what happens in skin after invasion by bacteria, viruses or fungi. The mechanism of local immune response developed in skin during the evolution and is highly conserved and efficient in elimination of foreign antigens. This is why the take of a skin allograft is so difficult and immunosuppressive measures applied after allogeneic skin transplantation remain so ineffective. Authors present their results of studies on the human skin immune humoral and cellular factors, underlining their specificities and differences compared with blood. They also analyze the role of non-immunological factors, such as tissue fluid formation and lymph flow in transportation of alloantigen to the lymph nodes. The migratory properties of immune cells are an indispensable factor in transfer of alloantigen to the lymph nodes. Understanding of the evolutionarily developed immune events in skin may allow to analyze the process of skin allograft rejection and can give hints for more effective immunosuppressive policy.

Pathways of antigen traffic from skin allotransplant to recipient lymph nodes--an evolutionarily developed route for initiation of rejection of foreign antigens.

In the previous studies we showed that vascularized bone marrow graft (VBMtx) in transplanted rat hind limb brings about complete repopulation of syngeneic recipient BM cavities and lymphoid organs within 10 days. Transplantation of an equivalent number of bone marrow cells (BMC) in suspension did not produce repopulation until day 30. In this study we present data on transplantation of allogeneic VBM and compare them with those obtained in a syngeneic combination. In the LEW or BN to LEW combination BM cells were labelled with 51Cr, injected i.v., 24 h later the hind limb was amputated and transplanted to a LEW rat. BM cells emigrated from the transplanted limb to the recipient and distributed in BM cavities and lymphoid tissues. In the LEW to LEW combination the level of radioactivity in recipient tibia was after 24 h 0.85, in spleen 2.43, in mesenteric lymph node 0.52%/g of tissue, whereas in the BN to LEW model it was 0.11, 1.83 and 0.15%, respectively. The calculated numbers of BM cells which populated recipient tissues were 8-10-times lower in the allogeneic compared with syngeneic combination. This was probably due to the nonspecific elimination of some subsets of BM cells (allogeneic BMC cytotoxicity). Administration of anti-asialo GMI antiserum to the recipient abrogated the cytotoxic effect. Taken together, major differences in kinetics of seeding and repopulation of BMC from VBMTx were found. Elimination of recipient NK cells with AAGMI antiserum attenuated the nonspecific cytotoxic effect. This protocol allows protection of the grafted BMC and increases the efficacy of the transplant.

Body distribution of syngeneic and allogeneic cells from vascularized bone marrow graft.

Cytotoxic sinusoidal lymphocytes of liver transplant are effective against circulating tumor cells.

The physiologic nonimmune factors necessary for alloantigen transport from skin graft to regional lymph nodes.

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Pathways of antigen traffic from skin allotransplant to recipient lymph nodes--an evolutionarily developed route for initiation of rejection of foreign antigens.

Body distribution of syngeneic and allogeneic cells from vascularized bone marrow graft.

Cytotoxic sinusoidal lymphocytes of liver transplant are effective against circulating tumor cells.

The physiologic nonimmune factors necessary for alloantigen transport from skin graft to regional lymph nodes.