Colon cancer cells acquire immune regulatory molecules from tumor-infiltrating lymphocytes by trogocytosis

Cancer cells can develop an immunosuppressive tumor microenvironment to control tumor-infiltrating lymphocytes. The underlying mechanisms still remain unclear. Here, we report that mouse and human colon cancer cells acquire lymphocyte membrane proteins including cellular markers such as CD4 and CD45. We observed cell populations harboring both a tumor-specific marker and CD4 in the tumor microenvironment. Sorted cells from these populations were capable of forming organoids, identifying them as cancer cells. Live imaging analysis revealed that lymphocyte membrane proteins were transferred to cancer cells via trogocytosis. As a result of the transfer in vivo, cancer cells also acquired immune regulatory surface proteins such as CTLA4 and Tim3, which suppress activation of immune cells [T. L. Walunas et al., Immunity 1, 405–413 (1994) and L. Monney et al., Nature 415, 536–541 (2002)]. RNA sequencing analysis of ex vivo–cocultured splenocytes with trogocytic cancer cells showed reductions in Th1 activation and natural killer cell signaling pathways compared with the nontrogocytic control. Cancer cell trogocytosis was confirmed in the patient-derived xenograft models of colorectal cancer and head and neck cancer. These findings suggest that cancer cells utilize membrane proteins expressed in lymphocytes, which in turn contribute to the development of the immunosuppressive tumor microenvironment.

Lipid specificity of the immune effector perforin

Perforin is a pore forming protein used by cytotoxic T lymphocytes to remove cancerous or virus-infected cells during immune response. During the response, the lymphocyte membrane becomes refractory to perforin...

Lymphocyte plasma membrane blebbing in patients with atherosclerosis of the main arteries and ischemic diabetic foot

Aim: to assess the blood flow state and the lymphocyte plasma membrane blebbing in atherosclerosis of the lower limb arteries and the ischemic diabetic foot (IDF).Patients and Methods: 75 patients (51 (68%) of them — women) underwent a prospective study with IDF and signs of chronic obliterating disease of lower limb arteries. In the majority of cases (92%), IDF occurred in the setting of type 2 diabetes mellitus. Blood circulation disorder corresponded to the stage II–III Fontaine–Pokrovsky classification, ulcerative defects — to the PEDIS grade 1–2 without signs of infection and with signs of local inflammation. The control group consisted of 25 healthy patients. Blood flow state (using Doppler ultrasound of the lower limb arteries) and diabetes mellitus compensation degree (by the level of glycated hemoglobin), as well as the lymphocyte membrane state were evaluated.Results: 72% of patients had a total occlusion of tibial and foot segments, 28% — stenosis. The level of glycated hemoglobin was 10.3 [8.5; 14.3]%, which indicated insufficient compensation of carbohydrate metabolism disorders. Total and terminal blebbing was 30.1 [25.4; 33.2]% and 15.8 [11.8; 18.4]%, which was 3 and 5 times higher than the control group, respectively. A high positive correlation was observed between the level of glycated hemoglobin and total (rS=0.72; p=0.001) and terminal (rS=0.78; p=0.001) lymphocyte membrane blebbing.Conclusion: given the presence of a high correlation between the indicator of glycated hemoglobin and lymphocyte plasma membrane blebbing, an increase in glycated hemoglobin can be used as a marker for the development of endothelial insufficiency in atherosclerosis of the lower limbs and IDF. At the same time, the level of total and terminal blebbing can be considered as a pathogenetic marker of macroangiopathy. KEYWORDS: diabetes mellitus, atherosclerosis, ischemia, hemodynamics, blebbing, glycated hemoglobin.FOR CITATION: Dunaevskaya S.S., Khachatryan A.T., Deulina V.V. Blebbing of plasma membrane of lymphocytes in patients with atherosclerosis of main arteries and ischemic form of diabetic foot syndrome. Russian Medical Inquiry. 2020;4(7):452–456. DOI: 10.32364/2587-6821-2020-4-7-452-456.

STUDY OF MULTIPLE SCLEROSIS PATHOGENESIS AS THE BASIS OF ITS TARGET THERAPY

Aim. To study the antigen-presenting ability of B-cells, class IV semaphorin Sema4D (CD100) and CD72 receptor expression in the immune system of patients with multiple sclerosis (MS); to study the interaction between the KIF1B gene polymorphisms and the variants of response to preparation, changing the course of multiple sclerosis in MS patients. Materials and methods. Patients with the established diagnosis of “Multiple sclerosis” by McDonald criteria 2010 with remitting type of the disease course were examined. Clinical method, psychometric testing, immune-enzyme analysis, immunologic method, PCR technique were used. Results. Among patients with MS, the antigen-presenting function of B-lymphocytes was changed, semaphorin Sema4D/CD100 expression level on T-lymphocyte membrane was elevated, CD72 receptor expression on B-lymphocyte membrane was decreased. The studied phenomena are associated with a number of clinical characteristics that permits to consider them to participate in the pathogenesis of this disease. Conclusions. Pathogenetic characteristics of multiple sclerosis are added by new data, which can be the targets for therapeutic strategies in the form of using anti-Sema4D- and anti-B-lymphocytic antibodies as immunomodulating therapy of MS.

Camouflaging iRGD-EGFR anchored human cytotoxic T-lymphocyte membranes to the surface of nanoparticles combined with low-dose irradiation: New approach to enhance drug-delivery targeting in gastric cancer.

e14076 Background: We report a biomimetic delivery platform based on human cytotoxic T-lymphocyte membranes. In this platform, T-lymphocyte membranes were camouflaged to the surface of poly-lactic-co-glycolic acid nanoparticles, with local low-dose irradiation (LDI) as a chemoattractant. These carriers were further anchored with the recombinant protein anti-EGFR-iRGD, improving tumor accumulation, facilitating tumor uptake. Methods: The T-lymphocyte membrane coating was verified by dynamic light scattering, transmission electron microscopy and confocal laser scanning microscopy. The particle phagocytosis study was performed using a human phagocytic cell line. In vivo NIR fluorescence imaging was performed to monitor the route of nanoparticles. EGFR expression of tumor cells was tested before and after LDI. Results: This new platform reduced phagocytosis of macrophages by 23.99% (p = 0.002). iRGD-EGFR anchored T-lymphocyte membrane-encapsulated nanoparticles accumulated in tumor site more than unfunctionalized groups, while LDI significantly enhanced the targeting ability. LDI could up-regulate EGFR expression on tumor cells, which was important in the process of localization of iRGD-EGFR anchored T-lymphocyte membrane-encapsulated nanoparticles in tumors. Conclusions: This new platform included both the long circulation time and tumor sites accumulation ability while LDI could significantly enhance the tumor accumulation ability.