B lymphocyte is an important component of the human immune system and it has a role in the process of the body's specific immunity. In recent years, the research on B cells and tumor immune escape has rapidly progressed. Studies have shown that different types of B cells play different roles in tumor microenvironment through a variety of mechanisms. B cells in the tertiary lymphatic structure promote anti-tumor immunity, while regulatory B cells promote tumor immune escape. Antibody drugs targeting B cells are a promising direction for tumor immunotherapy.
B-Lymphocytes/pathology* ; Humans ; Immunotherapy ; Neoplasms/therapy* ; Tumor Escape ; Tumor Microenvironment

OBJECTIVETo investigate the apoptosis of NK cells induced by the erythroleukemia cell line K562 in vitro.

METHODSPrimary NK cells isolated from the peripheral blood of healthy donors by magnetic-activated cell sorting were cultured with stem cell medium containing recombinant human interleukin-2 (rhIL-2). The NK cells and K562 cells were mixed and co-cultured at different E:T ratios for different time lengths. The apoptosis of NK cells and K562 cells were detected using PE-AnnexinV/7-AAD labeling and flow cytometry.

RESULTSThe purity of isolated NK cells reached (93.99∓4.22)%. At the same E: T ratio, the apoptotic rate of NK cells induced by K562 cells increased significantly with time. As the E:T ratio reduced, the apoptotic rate of the NK cells increased and their cytotoxic activity against K562 cells was attenuated.

CONCLUSIONK562 cells can induce the apoptosis of activated NK cells, which is one of the probable mechanisms of immune escape of tumors.

Immune therapy has become the fourth approach after surgery, chemotherapy, and radiotherapy in cancer treatment. Many immune checkpoints were identified in the last decade since ipilimumab, which is the first immune checkpoint inhibitor to cytotoxic T-lymphocyte associated protein 4, had been approved by the US Food and Drug Administration (FDA) for the treatment of unresectable or metastatic melanoma in 2011. The use of several antibody drugs that target PD1/PD-L1 for various cancer treatments has been approved by the FDA. However, fewer people are benefitting from immune checkpoint inhibitor treatment in solid cancers. Approximately 80% of patients do not respond appropriately because of primary or acquired therapeutic resistance. Along with the characterization of more immune checkpoints, the combinatory treatment of multiimmune checkpoint inhibitors becomes a new option when monotherapy could not receive a good response. In this work, the author focuses on the combination therapy of multiple immune checkpoints (does not include targeted therapy of oncogenes or chemotherapy), introduces the current progression of multiple immune checkpoints and their related inhibitors, and discusses the advantages of combination therapy, as well as the risk of immune-related adverse events.
Combined Modality Therapy ; Humans ; Immune Checkpoint Inhibitors ; Immunotherapy ; Melanoma/drug therapy* ; Tumor Escape

Human papillomavirus infection is often transient and spontaneously reversible. High-risk human papillomavirus persistence is the major cause of cancerous transformation in several tissues. For prophylactic vaccines there is first clinical evidence of effectivity (ie, 100% protection from HPV infection and dysplasia by virus-like particle (VLP) vaccine-induced neutralizing antibodies). Also, Therapeutic vaccines have entered clinical evaluation. While prophylactic VLP vaccines are immunogenic per se, therapeutic vaccines will need further adjuvants to guide T cell differentiation, expansion, survival, and homing to tumor sites. To enhance clinical outcome of successful T cell induction in patients, the susceptibility of the tumor cells for lysis must be addressed in the future, since tumor immune evasion is a severe problem in cervical cancer. Both preventive and therapeutic human papillomavirus vaccinations will probably change our approach to the screening and therapy of human papillomavirus-related diseases in the next few years. The mass vaccination of adolescent patients should lower the frequency of these very frequently lethal infections.
Adolescent ; Cell Differentiation ; Humans ; Mass Screening ; Mass Vaccination ; Papillomavirus Infections ; Tumor Escape ; Uterine Cervical Neoplasms* ; Vaccination ; Vaccines

This study was aimed to investigate the mechanism of indoleamine 2, 3-dioxygenase (IDO) activity in acute myeloid leukemia cells contributing to tumor immune escape. Myeloid leukemia cells were isolated from bone marrow of 23 patients with acute myeloid leukemia (AML) and IDO expression was detected by immunochemistry and RT-PCR methods. Then mixed lymphocyte reaction (MLR) of one way was carried out, leukemia cells were used as stimulating cells and T-lymphocytes were used as reactive cells in culture with or without 1-MT. T-lymphocyte proliferation rate was determined by MTT assay and IDO activity in supernatant of MLR was detected by high-performance liquid chromatography (HPLC). The results showed that IDO expression was found in 17 out of 23 cases of acute myeloid leukemia cells; IDO enzyme activity in leukemia cells inhibited T-lymphocyte proliferation in MLR cultures. It is concluded that IDO activity expressing in leukemia cells can suppress T-lymphocyte proliferation responses, which may be contributing to tumor immune escape.
Cell Proliferation ; Humans ; Immune Tolerance ; Indoleamine-Pyrrole 2,3,-Dioxygenase ; metabolism ; Leukemia, Myeloid, Acute ; enzymology ; immunology ; pathology ; T-Lymphocytes ; cytology ; immunology ; Tumor Cells, Cultured ; Tumor Escape ; immunology

In order to investigate the inhibition role of anti-Fas hammerhead ribozyme on Fas expression and Fas-mediated apoptosis in CTLL-2 cells (mouse CTL cell line), and to explore a new way for enhancing the ability of T cells against Leukemia in donor lymphocytes infusion, CTLL-2 cells were transfected with pEGFP-RZ596 and pEGFPC1 (mock-transfected) via electroporation. Fas expression on CTLL-2 cells was detected by RT-PCR and Western blot. The killing effect of CTL against WEHI-3 (mouse acute myelomonocytic leukemia cell line) highly expressing FasL in vitro was detected by MTT assay. The caspase-3 proteolytic activity and the apoptosis rate of CTLL-2 cells were detected by means of BD AproAlert Caspase-3 Colorimetric kit and FITC labeled Annexin-V apoptosis detecting kit respectively. The results showed that the anti-Fas ribozyme could be successfully introduced into mouse CTLL-2 cells; Fas expression on the surface of cells transfected with the ribozyme was obviously decreased, in comparison with control and mock-transfected cells; after cocultured with WEHI-3 cells, the viability of CTLL-2 cells transfeced with the ribozyme was significantly increased, as compared with other two groups; caspase-3 activity and apoptosis rate of the ribozyme-transfeced cells were significantly decreased, the killing effect of CTLL-2 transfected with the ribozyme was stronger than that of other groups. It is concluded that anti-Fas ribozyme can remarkably decrease Fas expression on CTLL-2 cells, so as to avoid Fas-mediated apoptosis by Fas ligand on WEHI-3 cells, and to enhance their killing activity against WEHI-3 cells, as a result, the immune escape of acute myelomonocytic leukemia was depressed.
Animals ; Cell Line ; Fas Ligand Protein ; immunology ; Leukemia, Myelomonocytic, Acute ; immunology ; Mice ; RNA, Catalytic ; T-Lymphocytes, Cytotoxic ; cytology ; immunology ; Tumor Cells, Cultured ; Tumor Escape ; genetics ; immunology

OBJECTIVE: To observe the expression of Fas receptor and ligand in human laryngocarcinoma cell line, Hep-2 and to investigate the possible mechanism of immune escape through Fas/FasL pathway in Hep-2 cell. METHOD: The mRNA and protein expressions of Fas and FasL in Hep-2 cell were analyzed by RT-PCR and flow cytometry (FCM). Growth curve of Jurkat cell was drawer based on the results of MMT, and apoptosis of Jurkat cell were determined by FCM and Hoechst 33342 staining after coculturing with Hep-2 cell. RESULT: The expressions of Fas and FasL in Hep-2 cell line were evaluated by flow cytometry and the mean fluorescence intensity were (32.91 +/- 5.6) and (25.57 +/- 7.1) respectively. After coincubation with Hep-2 cell (1 X 10(9)/L), the apoptosis rates of Jurkat cells were (38.95 +/- 0.11) % and (13.28 +/- 0.14) %, with planting concentration at 1 x 10(8)/L and 5 x 10 (8)/L respectively. In contrast, the apoptosis rate of Jurkat cultured separately was (7.53 +/- 0.17)%. The proliferation of Jurkat cell was obviously inhibited after coculture. However, the apoptosis rate was significantly decreased after adding neutralizing antibody of FasL. CONCLUSION Laryngocarcinoma cell could induce apoptosis of T lymphocytes through Fas-FasL system, thus it provided a potential mechanism to escape from immune surveillance of host.
Apoptosis ; Cell Line ; immunology ; Cell Line, Tumor ; Fas Ligand Protein ; metabolism ; Flow Cytometry ; Humans ; T-Lymphocytes ; immunology ; Tumor Escape ; fas Receptor ; metabolism

Exosomes are nanometer sized membrane vesicles, released in the extracellular milieu following the fusion of the external membrane of multivesicular body (MVB) with plasma membrane. They perform a certain function in immune regulation. Exosomes have been shown to be released by cells of hematopoietic and non-hematopoietic origin. Tumour-derived exosomes (TEX) exist in the supernatant of tumour cells, plasma and malignant effusions of tumour patients. They contain native candidate tumour associated antigen and are capable of transferring antigens to T lymphocytes, therefore efficiently promoting cytotoxic T lymphocyte (CTL) activation and producing antitumor immunity. However, recent evidence shows that tumor exosomes may induce immunologic tolerance and even activate immunosuppression which makes tumour escape from the immune surveillance of the host immune system. In addition, tumor exosomes may mediate a growth-promoting effect on tumor cells. These discrepancies are almost certainly due to differences in the phenotype of the exosomes.
Antigen-Presenting Cells ; immunology ; Antigens, Neoplasm ; immunology ; Cytoplasmic Vesicles ; immunology ; Endosomes ; immunology ; metabolism ; Exosomes ; immunology ; Humans ; Neoplasms ; immunology ; T-Lymphocytes, Cytotoxic ; immunology ; Tumor Escape

OBJECTIVE: To investigate the expression of ligand 1 of programmed death-1 in human nasopharyngeal carcinoma (NPC), the relationship between their expression and the clinicopathological features. METHOD: Immunohistochemistry was performed to assess the expression of PD-L1 in 59 cases of NPC tissues and 10 cases of normal nasopharyngeal tissue. RT-PCR was used to investigate the mRNA expression of PD-L1 gene in 30 NPC samples and 10 cases of normal nasopharyngeal tissues. RESULT: In case of tissues of nasopharyngeal carcinoma, the positive expression rate of PD-L1 protein and PD-L1mRNA were 67.8% (40/59) and 66.6% (20/30) respectively, while there were no PD-L1 detectable in normal nasopharyngeal tissues. The expression of PD-L1 was significantly correlated with clinical TNM stage and lymphatic metastasis (P <0.05). However, no significant correlation was founded between the expression of PD-L1 and age and sex (P >0.05). CONCLUSION PD-L1 is overexpressed in nasopharyngeal carcinoma, PD-L1 maybe play a certain role in carcinogenesis and progression of nasopharyngeal carcinoma and turn into a new target of immunotherapy of nasopharyngeal carcinoma.
Adult ; Aged ; Antigens, CD ; metabolism ; Apoptosis ; B7-H1 Antigen ; Female ; Humans ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; immunology ; metabolism ; pathology ; Tumor Escape

B7-H1, a recently described member of the B7 family of costimulatory molecules, is thought to be involved in tumor immune escape by inducing T-cell apoptosis. In order to investigate the relationship between B7-H1 and immune escape of bladder cancer, B7-H1 expression in 50 cases of bladder cancer was detected by using immunohistochemical method. Survival curves were constructed using the Kaplan-Meier method and independent prognostic factors were evaluated using the Cox regression model. Our results showed that the positive rate of B7-H1 immunostaining in normal bladder tissue and bladder cancer was 0 and 72% respectively. The expression of B7-H1 was strongly associated with the pathological grade, clinical stage and recurrence (P<0.05). The survival rate was significantly lower in patients with B7-H1 positive group than in those with B7-H1 negative group and multi-variable analysis revealed that B7-H1 could be regarded as an independent factor in evaluating the prognosis of bladder cancer. It is concluded that the expression of B7-H1 is strongly associated with neoplastic progression and prognosis of bladder cancer. The manipulation of B7-H1 may become a beneficial target for immunotherapy in human bladder cancer.
Antigens, CD/genetics ; Antigens, CD/*metabolism ; Antigens, CD80/genetics ; Antigens, CD80/*metabolism ; Prognosis ; Tumor Escape/*genetics ; Urinary Bladder Neoplasms/*immunology ; Urinary Bladder Neoplasms/metabolism