Search

Purpose Most malignant effusion are secondary to metastases to the pleura or peritoneum and portend poor oncological outcomes. Malignant effusion have different tumor microenvironment from primary tumor, containing a variety of cytokines and immune cells and directly contacting with tumor cells. However, the characteristic of CD4+ T cells and CD8+ T cells in malignant effusion remains unclear. Methods Malignant effusion including peritoneal ascites and pleural fluid from thirty-five patients with malignant tumor were collected and compared with matched blood. A detailed characterization of CD4+ T cells and CD8+ T cells in malignant effusion were conducted using flow cytometry and multiple cytokines assay. Results The concentration of IL-6 in malignant effusion was significantly higher than in blood. A substantial portion of T cells in malignant effusion were CD69+ and/ or CD103+ Trm cells. Most CD4+T and CD8+T cells in malignant effusion were exhausted T cells which expressed lower levels of cytokines, cytotoxic molecules and markedly higher levels of inhibitory receptor PD-1 compared with in blood. Conclusion Our study is the first to identify the presence of Trm cells in malignant effusion and will lay the foundation for future research on anti-tumor immunity of Trm cells in malignant effusion.

Despite the concern of within-tumor genetic diversity, this diversity is in fact limited by the kinship among cells in the tumor. Indeed, genomic studies have amply supported the ‘Nowell dogma’ whereby cells of the same tumor descend from a single progenitor cell. In parallel, genomic data also suggest that the diversity could be >10-fold larger if tumor cells are of multiple origins. We develop an evolutionary hypothesis that a single tumor may often harbor multiple cell clones of independent origins, but only one would be large enough to be detected. To test the hypothesis, we search for independent tumors within a larger one (or tumors-in-tumor). Very high density sampling was done on two cases of colon tumors. Case 1 indeed has 13 independent clones of disparate sizes, many having heavy mutation burdens and potentially highly tumorigenic. In Case 2, despite a very intensive search, only two small independent clones could be found. The two cases show very similar movements and metastasis of the dominant clone. Cells initially move actively in the expanding tumor but become nearly immobile in late stages. In conclusion, tumors-in-tumor are plausible but could be very demanding to find. Despite their small sizes, they can enhance the within-tumor diversity by orders of magnitude. Such increases may contribute to the missing genetic diversity associated with the resistance to cancer therapy.

Peri-engraftment respiratory distress syndrome (PERDS) is a kind of potentially life-threatening complication of autologous stem cell transplantation (ASCT). PERDS is characterized by fever, dyspnea, and hypoxemia during neutrophil engraftment. In order to identify the high-risk factors for PERDS, we retrospectively analyzed 260 patients with lymphoma undergoing ASCT in recent five years. The conditioning regimen was BuCyE (busulfan, cyclophosphamide, and etoposide). There were 16 patients (6.1%) diagnosed as PERDS. In multivariate analysis, prior anti-programmed death-1 (PD-1) therapy (hazard ratio [HR] = 8.852, 95% confidence interval [CI]: 2.954-26.527, P < 0.001) and history of pulmonary disease (HR = 3.718, 95% CI: 1.197-11.545, P = 0.023) were independent risk factors for PERDS. Patients with prior anti-PD-1 therapy (n = 31) had higher incidence of engraftment syndrome (77.4% vs. 33.4%, P < 0.001), PERDS (25.8% vs. 3.5%, P < 0.001), and transplant-related mortality (9.7% vs. 0.4%, P < 0.001), compared with those without prior anti-PD-1 therapy (n = 229). Subgroup analysis showed that sintilimab seemed to be associated with higher incidence of PERDS (42.9% vs. 11.8%, P = 0.06) compared with non-sintilimab group (pembrolizumab or toripalimab). C-reactive protein might be a feasible early predictor for PERDS. In conclusion, our study suggests that prior anti-PD-1 therapy may be a strong risk factor for life-threatening PERDS in patients with lymphoma undergoing ASCT.

At present, autologous stem cell transplantation (ASCT) is considered as an optional consolidation therapy for natural killer/T-cell lymphoma (NKTCL). However, the high-risk patients undergoing ASCT are not clear enough. In this study, 56 patients with advanced staged or relapsed/refractory (R/R) NKTCL undergoing ASCT were reviewed. All patients achieved clinical complete response (CR) before ASCT. The median follow-up time was 36 months (range, 3-192 months). The three-year overall survival (OS) and three-year progression-free survival (PFS) were 70.2% and 56.5%, respectively. The independent prognostic factors for OS included prior testis involvement and pre-ASCT EBV-DNA. Patients without prior testis involvement and negative pre-ASCT EBV-DNA (group A) had better three-year OS (86.3% vs. 47.6%

Background: Vitamin C (VitC) has been proposed as a potential anti-cancer agent for prolonging progression-free survival (PFS) and overall survival (OS) in non-small-cell lung cancer (NSCLC) patients. However, VitC has only been shown to be effective for some patients, and the mechanism in those who have benefitted from it remains unknown. We aimed to explore whether gene expression could predict IVC benefit for patients with NSCLC. Methods: H1299 and PC9 cells were treated with VitC and high-throughput sequencing was used for screening differential genes. Data from the Kaplan-Meier Plotter and the Human Protein Atlas databases were used for analysis of patient prognoses. In a retrospective study, 153 NSCLC patients from our Cancer Center were selected and divided into a control group (n = 81) and VitC group (n = 72) for immunohistochemical staining and prognosis analysis. Results: As a result, ZNF507, DLX4, and DDIT4 were found to be upregulated, and SERPINB7, TMEM158 and SERPINE1 downregulated in NSCLC cell lines following VitC treatment. Combined patient data from the cohort analysis and online databases revealed that the downregulated genes, but not upregulated genes, presented an unfavorable prognostic predictor of OS in NSCLC patients. Further analysis showed that the combined three genes were more efficient at predicting survival than individually (AUC=0.77, 95%CI, 0.63-0.90). Moreover, high expression of SERPINB7, TMEM158, and SERPINE1 in resected tumour- tissues before VitC treatment was found to be associated with prolonged OS in patients with NSCLC who were treated with VitC. Conclusion: Overall, these data revealed that SERPINB7, TMEM158, and SERPINE1 formed a novel NSCLC prognosis gene set and could serve as a potential therapeutic target as well as predictive factor for VitC treatment in patients with NSCLC. Trial registration: Retrospectively registered (No: 2/2021-PRE-48) on July 13, 2021.

Objective To evaluate the efficacy and safety of stent placement combined with intraluminal radiofrequency ablation (intra-RFA) and hepatic arterial infusion chemotherapy (HAIC) for patients with advanced biliary tract cancers (Ad-BTCs) and biliary obstruction (BO). Methods We retrospectively reviewed data for patients with Ad-BTCs and BO who underwent stent placement with or without intra-RFA and HAIC in three centres between November 2013 and November 2018. The stent patency time (SPT), overall survival (OS), and adverse events (AEs) were analysed. Results Of the 135 enrolled patients, 64 underwent stent placement combined with intra-RFA and HAIC, while 71 underwent only stent placement. The median SPT was significantly longer in the combination group (8.2 months, 95% confidence interval [CI]: 7.1–9.3) than in the control group (4.3 months, 95% CI: 3.6–5.0; p < 0.001). A similar result was observed for OS (combination: 13.2 months, 95% CI: 11.1–16.5; control: 8.5 months, 95% CI: 7.6–9.6; p < 0.001). The incidence of AEs related to biliary tract operation was not significantly different between the two groups (p > 0.05). The most common AE and serious AE related to HAIC were alanine aminotransferase elevation (24/64; 37.5%) and thrombocytopenia (8/64; 12.5%), respectively. All AEs were tolerable, and there was no death from AEs. Conclusions Stent placement combined with intra-RFA and HAIC may be a safe, potential treatment strategy for patients with Ad-BTCs and BO. Key Points • Advanced biliary cancers (Ad-BTCs) with biliary obstruction (BO) can rapidly result in liver failure and cachexia with an extremely poor prognosis. • Stent placement combined with intraluminal radiofrequency ablation and hepatic arterial infusion chemotherapy may be safe and effective for patients with Ad-BTCs and BO. • The long-term efficacy and safety of the combined treatment is promising.

Hemophagocytic syndrome (HPS) is a fatal hyperinflammatory disease with a poorly understood mechanism that occurs most frequently in extranodal natural killer/T cell lymphoma (ENKTL). Through exome sequencing of ENKTL tumor-normal samples, we have identified a hotspot mutation (c.419T>C) in the evolutionarily conserved signaling intermediate in Toll pathway (ECSIT) gene, encoding a V140A variant of ECSIT. ECSIT-V140A activated NF-κB more potently than the wild-type protein owing to its increased affinity for the S100A8 and S100A9 heterodimer, which promotes NADPH oxidase activity. ECSIT-T419C knock-in mice showed higher peritoneal NADPH oxidase activity than mice with wild-type ECSIT in response to LPS. ECSIT-T419C-transfected ENKTL cell lines produced tumor necrosis factor (TNF)-α and interferon (IFN)-γ, which induced macrophage activation and massive cytokine secretion in cell culture and mouse xenografts. In individuals with ENKTL, ECSIT-V140A was associated with activation of NF-κB, higher HPS incidence, and poor prognosis. The immunosuppressive drug thalidomide prevented NF-κB from binding to the promoters of its target genes (including TNF and IFNG), and combination treatment with thalidomide and dexamethasone extended survival of mice engrafted with ECSIT-T419C-transfected ENKTL cells. We added thalidomide to the conventional dexamethasone-containing therapy regimen for two patients with HPS who expressed ECSIT-V140A, and we observed reversal of their HPS and disease-free survival for longer than 3 years. These findings provide mechanistic insights and a potential therapeutic strategy for ENKTL-associated HPS.

Macrophages are polarized into two functionally distinct forms, M1 and M2, in response to different microenvironment. Tumor-associated macrophages (TAMs) generally have M2 phenotype and promote tumor progression. Few studies to date have described the infiltration of M2-polarized macrophages in ovarian cancer. We used two macrophages markers, CD68 and CD163, to analyze the expression of TAMs and to clarify the relationship between the M2 form and survival in advanced ovarian cancer. Clinical data of 110 patients with stages III-IV epithelial ovarian cancer at Sun Yat-sen University Cancer Center between 1999 and 2007 were retrospectively reviewed. Immunohistochemical staining of CD68 and CD163 was performed. Correlations between macrophage density and patient survival were analyzed. Our data showed that no significant difference was observed in survival between patients in the high- and the low-CD68 expression groups. In contrast, the progression-free survival (PFS) rates ( p = 0.003) and overall survival (OS) rates ( p = 0.004) were significantly higher in the low-CD163 expression group than in the high-CD163 expression group, respectively. Similarly, we also observed significantly improved 3-year PFS (49.8% vs. 11.0%, p < 0.001) and OS (77.4% vs. 45.0%, p < 0.001) rates in patients in the low-CD163/CD68 ratio group when compared with the high-CD163/CD68 ratio group. Multivariate analysis identified the density of CD163-positive cells as well as the ratio of CD163/CD68 as negative predictors for PFS and OS, respectively. Our results show that the infiltration of CD163-positive M2 macrophages as well as activation of macrophages towards the M2 phenotype may contribute to poor survival in advanced ovarian cancer.

Interleukin (IL)-17 is the signature cytokine of T helper 17 cells. The role of IL-17 in the tumor microenvironment is still controversial. Few studies describing IL-17 expression in ovarian cancer have been reported. We have therefore analyzed the in situ tumor expression of IL-17 in advanced ovarian cancer and the possible correlation of IL-17 expression with tumor-associated macrophages (TAMs) and with survival in advanced ovarian cancer. Clinical data of 104 patients with stage III–IV epithelial ovarian cancer at the Sun Yat-sen University Cancer Center between 2000 and 2008 were retrospectively reviewed. Immunohistochemical staining of IL-17 and CD163 (marker for TAMs) was performed. Our data showed that levels of IL-17 were significantly increased in ovarian cancer compared with normal ovarian tissues (P

BACKGROUND: Extranodal natural killer/T-cell lymphoma, nasal type (ENKTL) is an aggressive form of non-Hodgkin lymphoma. up to now, optimal therapeutic strategies for ENKTL have not been fully defined yet. However, approximately 25-50% patients experience local relapse or systemic failure who receive RT alone. The addition of chemotherapy is emphasized to reduce the risk of recurrence. Therefore, we evaluated efficacy and safety of P-GEMOX regimen in patients with newly diagnosed stage I/II ENKTL. METHODS: We conducted this pilot study to evaluate the efficacy and safety of pegaspargase combined with gemcitabine and oxaliplatin (P-GEMOX) followed by extensive involved-field radiotherapy(EIFRT) in patients with stage I/II ENKTL. We enrolled 56 newly diagnosed stage I/II patients. All patients received P-G GEMOX chemotherapy. The P-GEMOX dosage was as follows: gemcitabine 1000 mg/m2 intravenous infusion in 30 minutes ondays 1 and 8; oxaliplatin 100 mg/m2 intravenous infusion in 2 hours on day 1; pegaspargase deep intramuscular injection of 2000 U/m2 at two different sites on day 1. The regimen was repeated every 3 weeks. Patients underwent 4 cycles of induction chemotherapy, followed by EIFRT. After achieving complete response (CR), partial response (PR), or stable disease (SD). EIFRT was 56 Gy in 28 fractions over 4 weeks. Primary EIFRT was delivered using 6-MeV linear accelerator using 3-dimensional conformal treatment planning. Clinical target volume (CTV) included gross tumor volume with a margin of at least 20mm and the bilateral nasal cavity, bilateral parasinusess. Planning target volume (PTV) included CTV with a 5mm margin. For stage IIE disease, CTV and PTV also included the involved the cervical lymph node area. RESULTS: The median follow-up was 35.2 months (range: 10.6-51.4 months). The objective response rates(ORR) of P-G GEMOX regimen was 89.3% (50/56), 35(62.5%) patients achieved CR and 15 (26.8%) patients achieved PR, respectively. After EIFRT, ORR increased to 94.6% (53/56), CR rate increased to 89.3% (50/56). The 4-year overall survival(OS) and progression-free survival(PFS) rate was 90.7¡À4.0% and 89.1¡À4.2% for the whole cohort. The OS and PFS of stage I patients were superior to patients with stage II (Figure1A,B). No treatment-related death was observed. No allergic reactions occurred. Common toxicities (>50%) were neutropenia (80.3%), thrombocytopenia (55.3%), hypoproteinemia (75.0%). Fibrinogen decrease rate was 44.6%. The most common grade III/IV toxicities (>10%) were granulocytosis (23.2%), thrombocytopenia (19.6%) and hypoproteinemia (10.7%). CONCLUSION: The P-GEMOX regimen followed by radical radiotherapy yielded very promising longterm survival for patients with stage I/II ENKTL with good tolerance. Further investigation of P-GEMOX in a larger series of patients, is required. Figure 1. Survival for different stage. (A) Overall survival(P =0.056). (B) Progression free survival (P =0.023). A. B. Figure 1. Survival for different stage. (A) Overall survival(P =0.056). (B) Progression free survival (P =0.023). / A. B. Figure 2. Figure 2. Disclosures No relevant conflicts of interest to declare.

Purpose Extranodal natural killer/T-cell lymphoma (ENKTL) is an aggressive form of non-Hodgkin's lymphoma. The prognosis for patients with advanced stages or relapsed/ refractory ENKTL is extremely poor. Optimal combined chemotherapy remain to be defined. Therefore, the purpose of this study is to evaluate efficacy and safety of P-GEMOX (Pegaspargase, Gemcitabine and Oxaliplatin) in patients with newly diagnosed stage III/IV or relapsed/refractory ENKTL. Patients and methods We retrospectively analyzed the effectiveness and toxicity of P-GEMOX in 60 patients with newly diagnosed stage III/IV and relapsed/refractory ENKTL between February 2008 and August 2014. The P-GEMOX dosage was as follows: Gemcitabine 1000 mg/m2 iv d1,d8; Oxaliplatin 100 mg/m2; d 1, Pegaspargase 2000 U/m2 im, two different sites. The regimen was repeated every three weeks for a maximum six cycles. Patients underwent autologous hematopoietic stem cell transplantation (ASCT) as consolidation if they achieved CR. Results 57 patients were available for evaluation of response. The objective response, complete remission(CR), of whole cohort were 73.7% (42/57), 36.8% (21/57), respectively. It can be easily administered in out-patients clinic. The median follow-up was 29.1 (range, 2.4¨C54.2 months). Median OS and PFS was 23.0 months (95% confidence interval [CI], 16.441-29.559) and 12.8 months(95% confidence interval [CI], 8.109-17.491), respectively. The 4-year OS and PFS rate was 43.0¡À7.3% and 36.5¡À6.9%, respectively (Figure1). There was no difference between newly diagnosed stage III/IV and relapsed/refractory in OS and PFS. The long term survival CR responders were superior to patients with other response, and there was significant difference between the three group(Figure 2, P50%): neutropenia (85.0%), thrombocytopenia (72.0%), hypoproteinemia (86.7%), and anorexia (63.3%). In addition, hypofibrinogenemia was 46.7%. The most common grade III/IV toxicities (>10%) were granulocytosis (31.6%), thrombocytopenia (26.67%) and hypoproteinemia (13.3%)(Table 1). Intracranial bleeding occurred in one patient during the first cycle with discontinuation of pegaspargase in the consecutive cycles. No treatment related death confirmed. Conclusion The P-GEMOX regimen is a safe and effective combination for newly diagnosed advanced and relapsed/refractory ENKTL. Promising long term outcome can be expected by addition of ASCT consolidation after response to induction chemotherapy. In comparison to other combined regimen in literatures, P-GEMOX is effective with less toxic, simplified and high cost-effective. Further clinical trials urgently needed. Table 1. Toxicities of whole cohort All cases (%) Grade 1/2 (%) Grade 3/4 (%) Toxicities Neutropenia 51(85.0) 32(53.3) 19(31.6) Thrombocytopenia 22(36.7) 15(25.0) 7(11.7) Anemia 43(71.6) 18(66.7) 3(5.0) lymphocytoponia 14(23.3) 12(20.0) 2(3.3) AST/ALT elevated 26(43.3) 22(36.7) 4(6.7) Hypoproteinemia 53(88.3) 48(84.9) 8(13.3) Fbg decrease 41(68.3) 39(65.0) 2(3.3) APTT prolong 16(26.7) 16(26.7) 0 Hyperglycemia 7(11.6) 7(11.6) 0 Total bilirubin elevated 9(15.0) 9(15.0) 0 Nausea 21(35.0) 21(35.0) 0 Anorexia 32 (53.3) 32 (53.3) 0 Vomiting 19(31.6) 19(31.6) 0 Allergic reactions 1(1.7) 1(1.7) 0 herpes zoster 3(5.0) 3(5.0) 0 Figure 1. 4-year OS and PFS of whole patients Figure 1. 4-year OS and PFS of whole patients Figure 2. Survival of whole patients, based on response Figure 2. Survival of whole patients, based on response Figure 3. OS: patients with ASCT vs. Non-ASCT Figure 3. OS: patients with ASCT vs. Non-ASCT Disclosures No relevant conflicts of interest to declare.

Backgroud It has been demonstrated that Natural/killer T-cell lymphoma (NK/TCL) derives from chronic EBV infection of nasopharynx. In recent years, IL-6 has been proved to be associated with a variety of inflammation-related malignancies in terms of carcinogenesis, tumor proliferation and metastasis. However, there hasn’t been any report about IL-6 on the pathogenesis and development of NK/TCL. Patients and Methods From January 2005 to December 2012, the paraffin sections of 91 patients with NK/TCL in Sun Yat-sen University Cancer Center were collected. The activation/expression of NF-ΚB(P50, P52, P65), IL-6,P-STAT3(Tyr705),BCL-2 in tumor microenviroment were investigated by immunohistochemistry. The NK/TCL cell lines were treated by IL-6(80ng/ml) and neutralizing IL-6 antibody, then the viability and apoptosis of lymphoma cell lines (NK-YS, SNK-6 and SNT-8) were assessed by CCK-8 and flow cytometry; and the expression of p-STAT3, BCL-2, BCL-XL, MCL-1, Survivin、p-ERK and p-AKT were examined by Western blot . Results Overall, ninety-one patients with NK/TCL were analyzed. There were 68 male patients. The median age was 43 years (range 10-68 years). There were 52, 14 and 25 patients diagnosed as stage I, II and IV disease, respectively. Sixty-one patients had B symptoms. The P52 activation was observed in the microenviroment of most patients, while P65 and P50 activation were observed in minority of patients. In patients with P52 activation, P52 activation was observed both in macrophages and lymphoma cells, and vice versa. IL-6 was primarily secreted by macrophages and tumor cells, and 69.2% (63/91) patients were positive (IL-6 secreting cells ≥ 10 / HP). The STAT3 activation was observed in 67.0% (61/91) of patients, most of which were combined with expression of BCL-2. The expression of P52、IL-6、P-STAT3、bcl-2 in the microenvironment of NK/TCL were in uniform (all positive or all negative). Patients with positive expression of IL-6 were associated with fever, advanced stage, high serum level of C-reactive protein (CRP), chemotherapy resistance and poor survival (P < 0.05). Comparing with blank control group and the neutralizing IL-6 antibody group, the cell viability and antiapoptosis ratio of NK-YS、 SNK-6、SNT-8 cells were higher in the IL-6 group (P Conclusions The NK-κB(P52)/IL-6/STAT3 pathway is activated in tumor microenvironment, and is associated with fever, advanced stage, high serum level of CRP in patients with NK/TCL. IL-6 could activate the JAK/STAT3 pathway in NK/T lymphoma cell lines, and promote lymphoma proliferation and anti-apoptosis. The activation of NK-κB(P52)/IL-6/STAT3 pathway may lead to chemotherapy resistance and poor survival in patients with NK/TCL. Disclosures: No relevant conflicts of interest to declare.

Background and Objective Natural killer/T-cell lymphoma (NK/TCL) is featured with inflammatory symptoms and poor prognosis. Currently, new treatment targets and modalities are urgently needed for patients with high risk NK/TCL. As one of the most important factors in the microenvironment of lymphomas, tumor-associated macrophages (TAM) may display either positive or negative effect on tumor proliferation and metastases, depending on the polarization of macrophages (M2 or M1 type). It is well established that the activation and differentiation of TAM are determined by different stimuli from the microenvironment. The characteristic cytokine spectrum of M1 type macrophages is high expression of IL-6 and IL-12, and low expression of IL-10. In contrast, the characteristic cytokine spectrum of M2 type macrophages is high expression of IL-10 and low expression of IL-12. Prior studies have revealed that IL-4, IL-10 and IL-13 are key cytokines which stimulate the differentiation from monocytes to M2 polarized TAM. Our study was designed to explore the cytokine spectrum secreted by NK/TCL and TAM in the microenvironment of NK/TCL. We aimed to prove that NK/TCL could induce the differentiation from monocytes to M2 polarized TAM, by secreting special cytokines. Material and Methods The cell lines involved in the study were as follows: the human NK/TCL cell lines (NK-YS, SNK-6 and SNT-8); the human diffuse large B-cell lymphoma cell line (OCI-LY8); and the human acute monocytic leukemia cell line (THP-1). We analyzed the cytokine spectrums in the supernatant of the cell lines mentioned above by using a multiplex suspension array (Bio-Plex Pro Human Cytokine 27-Plex Panel, Bio-rad). Then, we examined the cytokine spectrums in the supernatant of THP-1 cell lines which were cultured in the following groups of medium: A. Roswell Park Memorial Institute (RPMI) 1640 medium; B. RPMI 1640 medium with phorbol-12-myristate- 13-acetate (PMA, PMA can stimulate the activation of M1 polarized macrophages from THP-1 cell line); C. RPMI 1640 medium mixed with supernatants from NK/TCL cell lines; D. RPMI 1640 medium mixed with supernatant from the OCI-LY8 cell line. To balance the existing cytokines secreted by lymphoma cells, a same sample of medium mixed with the corresponding supernatants from lymphoma cell lines were used for baseline concentration as controls, respectively, in group C and D. Results There were a variety of elevated cytokines detected in NK/TCL cell lines, including: IL-1ra, IL-4, IL-6, IL-8, IL-10, IL-9, IL-13, IP-10, MCP-1 and IFN-¦A. There were no IL-4, IL-10 or IL-13 detected in the supernatant of OCI-LY8 cell line. The morphology and cytokine concentration of THP-1 cell lines in different groups were showed in Figure 1 and Table 1, respectively. In group B, the concentration of IL-1b was significantly higher than group A; In group C, the concentration of IL-1ra, IL-10 and IL-6 were significantly higher than group A, while the concentration of IL-12 was significantly lower, and the concentrations in group C gradually increased (IL-12 decreased) with time prolonged, which indicated a M2 polarization. There was no significant difference in terms of cytokine concentration between group A and group D (Table 1). Table 1. The cytokine spectrum of THP-1 cell lines in different groups. Group A Group B Group C Group D p-value Control PMA NK-YS SNK-6 SNT-8 OCI-LY8 IL-1b 1.97 129.02 25.36 27.94 23.58 1.82 0.01 IL-1ra 20.42 154.24 162.19 130.58 158.22 19.24 IL-6 2.58 426.40 240.14 168.25 299.33 2.18 0.001 IL-10 1.35 2.80 20.58 5.85 6.37 1.32 IL-12 16.58 40.19 13.24 12.01 13.87 15.9 Download : Download high-res image (57KB) Download : Download full-size image Figure 1. The morphology of THP-1 cell lines in different polarization (200X). A. undifferentiated monocytes (Group A); B. M1 type macrophages (Group B) there were pseudopodia and phagocytosed particles in macrophages; C. M2 type macrophages (Group C). Conclusions Our study suggests that the NK/TCL cell lines can secrete various cytokines. Some of these cytokines could induce the differentiation from monocytes to M2 polarized TAM, and the key cytokines might be IL-4, IL-10 and IL-13. The interactions between NK/TCL and TAM may provide novel targets for treatment of NK/TCL. Disclosures: No relevant conflicts of interest to declare.

Backgroud Natural/killer T-cell lymphoma (NK/TCL) was previously named as lethal midline granuloma. Most patients presented with inflammatory symptoms such as fever and necrosis, which was associated with poor survival. It is still unclear what exactly the role of severe inflammation on the pathogenesis and development of NK/TCL, and there has been few report about the serum cytokines profile and its clinical significance in patients with NK/TCL. Patients and Methods From January 2005 to December 2012, the serums and paraffin embed tissues of 59 patients with NK/TCL in Sun Yat-sen University Cancer Center were collected. The Human Cytokine 25-Plex Panel kits (Invitrogen) were used to detect the serum level of the cytokines. And the real-time quantitative polymerase chain reaction (RT-PCR) was employed for detection of the plasma EBV-DNA copies. Results Overall, fifty-nine patients with NK/TCL were analyzed. There were 44 male patients. The median age was 39 years (range 10-69 years). There were 37, 5 and 17 patients diagnosed as stage I, II and IV disease, respectively. Forty-one patients had B symptoms and ten patients were diagnosed hemophagocytic syndrome. Fifty-eight patients were followed up, the median follow-up time was 25 (0.2¨C70) months. Comparing with the 12 normal control cases, there were high proinflammatory cytokines and chemokines detected in most patients with NK/TCL(without hemophagocytic syndrome, HPS), including, interleukin-6 (IL-6)(2.56 (0.00-22.29) pg/ml), IL-1ra(88.98 (0.00-1210.05) pg/ml),interferon-¦Ã(IFN-¦Ã)(2.78 (0.00-61.60) pg/ml), IP-10 (41.85 (0.00-1057.41) pg/ml),MIG(49.90 (0.00-799.00) pg/ml), IL-10(0.43 (0.00-13.48)pg/ml), sIL-2R(168.82 (0.00-1916.61) pg/ml),IL-15(0.00(0.00-443.76) pg/ml)(datum express the median serum concentration of cytokines and their range). The serum levels of these cytokines and chemokines mentioned above dramatically increased in 10 patients with hemophagocytic syndrome. The serum concentration of these proinflammatory cytokines and chemokines was notably higher in patients with fever, advanced stage, and microenvironment NF-kB alternative pathway (P52) activation. In patients with P52 activation, the concentration of these cytokine were higher in those plasma EBV-DNA copies ≥103copy/ml (P≤¼0.05). Multivariate analysis showed that the Korean Prognostic Index (KPI)(P=0.003), the serum concentration of IL-6 (P=0.035) and IL-2R(P=0.044) were independent prognostic factors. High serum IL-6 and IL-2R correlates with poor survival. Twenty-nine patients with serum IL-6 level≤3.97pg/ml, had better survival, with 68.0±8.8% of 3-year overall survival (OS); while 3-year OS of the higher serum IL-6 group was 21.3±8.1% (P=0.001). Conclusion ≤°Our study indicate that patients with NK/TCL had special serum proinflammatory cytokines and chemokines profile, and these cytokines were notably higher in those with fever, advanced stage, the NF-kB alternative pathway activation in microenvironment, and EBV-DNA copies ≥103copy/ml. Moreover, high serum concentration of IL-6 and IL-2R were correlated with poor survival. Disclosures: No relevant conflicts of interest to declare.