黄芪多糖Fb对人血淋巴细胞免疫功能的影响

Chemotherapy and/or radiotherapy are believed to further lower the already low cellular immunologic response of cancer patients giving poorer prognosis. A number of Chinese medicinal herbs known as Fuzheng therapy (FZT), in which AM is an active one, are being used to enhance the natural host defence function in cancer patients. Among some fractions of AM polysaccharide extracts, FB was the strongest. In vitro restorative effects of FB in 18 normal healthy individuals and in 9 previously untreated advanced cancer patients are reported. Local graft versus host (GVH) reaction and blastogenic response of lymphocytes in vitro (BRL) were used as test index for T-cell function. GVH reaction nodules with a volume greater than or equal to 50 mm3 were considered as positive GVH reaction. FB 100 micrograms/ml induced a restored reaction in 18 normal donors with an increase in local GVH reaction from 69.6 +/- 20.8 mm3 to 148.9 +/- 40.8 mm3 (P less than 0.001) and in 9 cancer patients with an increase in local GVH reaction from 29.3 +/- 9.5 mm3 to 137.2 +/- 35.8 mm3 (P less than 0.001). The local GVH reaction of the 9 cancer patients went from negative to positive. FB on BRL was detected. 10 micrograms/ml of FB augmented the spontaneous 3H-TdR incorporation in the lymphocyte of 18 normal subjects from 310.2 to 910.9 counts per minute (cpm) and of 9 patients from 248.5 to 642.2 cpm, but the effects were not strong. The effect of single mitogen was not remarkable.(ABSTRACT TRUNCATED AT 250 WORDS)     

Partial restoration of local GVH reaction in cancer patients by depletion of theophylline-sensitive suppressor T-cells

Theophylline-resistant T-cell subpopulations were assessed in terms of numbers and function among patients with disseminated cancer, and compared to normal controls. Within the total E-rosetting T-cells (65 +/- 6.5% for normal donors versus 34 +/- 1.0% for cancer patients; P less than 0.001) the proportion of theophylline-resistant Te cells was 56 +/- 1.5% and 26.6 +/- 1.1%, respectively (P less than 0.001). This significant difference in distribution between theophylline-resistant (effector) and theophylline-sensitive (suppressor) cells in favor of the latter was also reflected by the poor performance of unseparated T-cells in the local GVH reaction. Thus, the mean GVH reaction among normal donors was 159 +/- 30 mm3 versus 44 +/- 28 mm3 among cancer patients (P less than 0.001). Removal of the theophylline-sensitive suppressor T-cells resulted in significant augmentation of the local GVH reaction among normal donors and in significant, although partial, immune restoration of the local GVH reaction in some patients but not in others. The mean local GVH reaction after removal of theophylline-sensitive suppressor T-cells was 196 +/- 89 mm3 among normal donors and 68 +/- 46 mm3 among cancer patients (P less than 0.05). This immune restoration following depletion of suppressor T-cells was only partial among cancer patients because of an apparent intrinsic defect in the capacity of their effector T-cells to exert vigorous local GVH reaction. In one small group of four patients, this intrinsic defect was so profound that even after removal of the theophylline-sensitive suppressor cells, the restoration of the local GVH reaction was negligible (12 +/- 10.8 mm3 versus 24 +/- 9.8 mm3; P greater than 0.1). The quantitative and qualitative changes in effector and suppressor T-cell distribution during the development of the malignant process and the possible interaction between them are discussed.     

Potent effects of the prostaglandin synthesis inhibitor indomethacin on the cellular immune response in gastrointestinal cancer patients

An increased level of prostaglandin E2, which is produced in carcinoma tissue, has been suggested to be involved in immunosuppression in cancer patients. This study examines the hypothesis in which the inhibition of prostaglandin production by a nonsteroidal anti-inflammatory agent, indomethacin, could modulate cancer-induced cellular immunosuppression. The experimental results demonstrated (i) a restoration of cellular immune reaction (NK activity of spleen monocytes) followed by tumor regression in subcutaneously transplanted colon adenocarcinoma 26-bearing BALB/c mice, which received 0.002% water solution as drinking water from day 0 or 7 of tumor transplantation, compared with indomethacin-untreated mice, (ii) an improved cellular immune response (PHA-and Con A-augmented lymphocyte blastogenesis, NK activity and LAK activity of peripheral venous blood monocytes) in 19 stomach cancer and 11 colorectal cancer patients before surgery, who received a daily oral dose of 75 mg indomethacin for 7 days, and in 8 colorectal cancer patients after curative surgery, who received a daily oral dose of 600 mg tegafur and 50 mg indomethacin for 1 month or longer, compared to patients without indomethacin treatment. It suggests, therefore, that the prostaglandin synthesis inhibitor, indomethacin, may restore cellular immunity, and may provide a good therapeutic tool against cancer of the gastrointestinal tract.     

The effect of indomethacin and leukinferon on the thromboxane B2 level in the blood plasma of patients with endometrial cancer in the perioperative period]

The paper discusses the effect of indomethacin, leukinferon as well as their combined effect on blood thromboxane B2 (TxB2) level in 40 endometrial cancer patients in the perioperative period. Perioperative treatment with indomethacin was followed by a significant decrease in blood TxB2 level before surgery and in the postoperative period. Treatment with leukinferon exerted similar effect which, however, was less pronounced than that of indomethacin. The effect was most apparent when the two drugs were combined. The influence of indomethacin and leukinferon on metabolism of arachidonic acid in tumor cells and those of the immune system of endometrial cancer patients are discussed as well possible role of eicosanoids in the pathogenetic mechanism of growth and dissemination of reproductive tumors.     

Indomethacin sensitive suppressor-cell activity in head and neck cancer patients. The role of the adherent mononuclear cell

Head and neck cancer (H&N CA) patients have known depression of cell-mediated immunity. There is suggestive evidence that prostaglandin (PGE2)-secreting cells may be a major factor. The authors have sought to determine the role of PGE2-releasing monocytes-macrophages in this immune depression by determining the effects of adherent cell depletion and by measuring the effects of indomethacin, a PGE2 synthetase inhibitor, on selected tests of lymphocyte function. Lymphocyte stimulation with phytohemagglutinin (PHA) (T-cell stimulant) and Staph phage lysate (SPL) (B-cell stimulant) was done in the presence of varying concentrations of indomethacin; the effect of adherent cell depletion also was determined. The study population included 45 patients with localized or locoregional squamous CA of the H&N and 40 controls. Results included the following: (1) lymphocyte stimulation responses to PHA and SPL were generally depressed in the CA patients versus controls; (2) incubation with indomethacin produced bivalent effects in both controls and CA patients, depending on the concentration of indomethacin and lymphocyte stimulant; incubation with optimum concentrations of indomethacin generally produced augmented responses in both study groups whereas high concentrations of indomethacin were suppressive; (3) the immune potentiating effects were not observed in older patients with advanced disease; and (4) removal of adherent leukocytes (mainly monocytes) also restored depressed lymphocyte responses. Although other factors also are operative, our data suggest that PGE2-secreting monocytes-macrophages may have a major role in the immune depression of H&N CA patients. Age and host effects of the cancer and the malnutrition common to these patients probably are involved also, although their singular contribution has not been measured. This depression is largely reversible by a PGE2 synthesis inhibitor, indomethacin, which suggests the potential value of in vivo administration of indomethacin to H&N CA patients as an adjunct.     

Inhibition of the growth of a murine transplantable tumor, colon 26, by the prostaglandin synthetase inhibitor, indomethacin

Cancer cells and macrophages produce large amounts of prostaglandin (PG) E2, which suppress cellular immune r action in tumor-bearing individuals. These findings raised a possibility that PG synthetase inhibitor can restore the immune reactivity against tumors. The anti-tumor activity of indomethacin, a potent PG synthetase inhibitor, by oral administration of 0.002% water solution as drinking water from the day 0 or 7 days after tumor transplantation was investigated in BALB/c or CDF1 (BALB/c X DBA/2) mice implanted subcutaneously with colon carcinoma 26 (10(6) cells) as a series of model studies for cancer treatment. The treatment with indomethacin substantially 1) inhibited the tumor growth, 2) prolonged the survival time, 3) caused a regression and disappearance of tumor with some cured mice and 4) reduced the levels of PGE2 and ornithine decarboxylase activity, a first rate limiting enzyme of polyamine synthesis in tumor tissue. Those anti-tumor activities were 5) reduced by a concomitant administration of PGE2 and 6) increased by a combined administration of an immunopotentiating agent, Picibanil (OK-432). The results indicate that indomethacin inhibited the synthesis of PGE2 in the tumor tissue, which suppress the non-specific cellular immune reaction against tumor cells, resulting in the regression and disappearance of tumor. PG synthetase inhibitor may be effective also against human cancer.     

Anti-leukaemia activity as a bystander effect of graft-versus-host reactions.

The production of graft-versus-host (GVH) reactions in (PVGc X Wistar) F1 hybrids by the transfer of PVGc spleen cells resulted in significant resistance of these recipients to a subsequent challenge with the PVGc leukaemia. Protection was markedly dependent on dose and timing of allogeneic cell transfer and was abrogated by irradiation of the cells prior to transfer. GVH activity was shown to be a prerequisite for induction of the protective effect but was equally effective when produced by the transfer of Wistar spleen cells in place of PVGc cells. These points, plus the fact that invitro investigations of possible immune mechanisms failed to demonstrate cytotoxic immunity in treated rats, suggested a nonspecific "bystander" effect as the mechanism of protection. The implications of such a mechanism are discussed.     

The immunomodulating role of indomethacin in the chemoradiation treatment of inoperable patients with lung cancer]

The immunocorrective effect of indomethacin in the course of chemoradiation treatment for inoperable lung cancer was established in a group of 117 patients. It manifested itself in an increase in T-lymphocyte level, normalization of their membrane structure and improvement in immunoregulatory function mainly due to a rise in T-helper/inductor level. Blood plasma-circulating immune complex concentration returned to normal. The concomitant administration of indomethacin during chemoradiation therapy improved subjective status of patients and tumor response but failed to increase survival.     

头孢地秦对肺癌患者细胞免疫系统的影响

目的 探讨头孢地秦对肺癌患者细胞免疫的增强作用。方法 选择肺癌并发呼吸系统感染患者４５例,同期选择呼吸系统感染患者１０例。检测各组外周血和肺泡局部细胞免疫指标。结果 （１）用头孢地秦的肺癌患者外周血中性粒细胞的硝基四唑氮蓝（ＮＢＴ）阳性率、ＮＫ细胞计数、ＣＤ４＾＋细胞计数、ＣＤ４＾＋／ＣＤ８＾＋比值、肺泡巨噬细胞（ＡＭ）吞噬中性红的吸光度（Ａ,旧称光密度ＯＤ）以及支气管肺泡灌洗液中ＩＬ－１β浓度均     

Suppression of Metastatic Murine Ovarian Cancer Cells by Transduced Embryonic Progenitor Cells

Ovarian cancer is the leading cause of death among gynecological malignancies. Chemotherapy alone is not sufficient to achieve long-term survival of the patient with advanced stage ovarian cancer. Although cancer immune therapy has long been expected as a new modality for ovarian cancer, very few trials have been clinically successful. One of the reasons for the failure in practical immune therapy is the immune-suppressive cancer microenvironment. We have reported that immune-suppressive molecules including PD-L1, Cox or ULBP-2 are expressed in human ovarian cancer, and they suppress local tumor immunity by disturbing CD8+T cell infiltration. Thus, we attempted to develop an immune therapy that can target multiple metastatic foci and increase CD8+T cell infiltration by altering local tumor environment. Endothelial progenitor cells (EPC) were transduced with the chemokine CCL19. When injected intravenously, this "immune-stimulatory EPC" was incorporated efficiently into local tumor vessels, and exerted an anti-tumor effect in a subcutaneous tumor model, a lung metastasis model and a peritoneal dissemination model. The anti-tumor effect was not observed when immunodeficient mice were used for the experiment, suggesting that the effect is mediated by immune cells. These results suggest that EPC are ideal carriers with which to deliver immune-stimulatory signals to multiple remote metastases. Alteration of local immune environment by this method may be used in the future for individualized cancer immune therapy.     

胃癌局部细胞因子表达谱分析

目的 探讨胃癌局部细胞因子表达的特点,为胃癌免疫治疗提供依据。方法 以相应非癌性黏膜组织为对照,采用高敏感放射性标记半定量RT－PCR技术,分析胃癌患者癌组织中纯化的CD4^ 、CD8^ T细胞亚群及上皮细胞的细胞因子表达谱。结果 胃癌组织与非癌性黏膜组织相比,CD4^ 和CD8^ T细胞亚群中均表现为Th2型细胞因子表达明显增加,Th1型细胞因子表达降低。其中癌组织CD8^ T细胞的IL－6、IL-8TNF－α的水平显著高于非癌性黏膜组织（P＝0．029,P＝0．022,P＝0．002）;胃癌组织的T细胞及癌性上皮细胞中细胞因子IL－10,TGFβ1和TNF－α的表达较非癌性黏膜组织增高。结论 胃癌局部Th1、Th2之间的平衡向Th2漂移,提示胃癌局部呈免疫抑制状态。CD8^ T细胞中细胞因子表达变化更为显著,提示CD8^ T细胞在胃癌局部免疫抑制发生中起主要作用。对不同细胞亚群细胞因子表达状况的了解有助于免疫治疗方案的设计。     

Effects related to indomethacin prolonged survival and decreased tumor-growth in a mouse-tumor model with cytokine dependent cancer cachexia

Tumor-bearing mice with two different locally growing malignant tumors (epithelial like, MCG 101; malignant melanoma, K1735-M2) were used to evaluate the putative role of prostaglandins for survival and local tumor growth in experimental cancer. Daily systemic injections of indomethacin (1 mu g/g bw) were used to block prostaglandin production in normal and T-cell deficient tumor-bearing nude mice. Tumor progression was determined by measurements of tumor weight, DNA-synthesis, cell cycle kinetics in vivo and in vitro (flow cytometry), tumor tissue concentrations of polyamines (putrescine, spermidine, spermine) and tumor tissue gene expression of growth regulating factors (IL-1 alpha, IL-6, TNF alpha, A,B-PDGF, EGF, VEGF, bFGF, TGF beta(3), angiogenin and transferrin receptor). Tumor tissue content of von Willebrandt factor VIII was estimated by immunohistochemistry. Indomethacin had no effect on survival, host nutritional state or local tumor growth in mice bearing the malignant melanoma with low PGE(2) production. In contrast, indomethacin prolonged survival, improved cachexia and decreased tumor growth in mice bearing the MCG 101 tumor with hundredfold higher prostaglandin tumor production, leading to elevated liver and muscle tissue as well as plasma concentrations of PGE(2). Indomethacin inhibited almost completely the high tumor PGE(2) production in MCG tumors, leading to prolonged potential doubling time for tumor growth in vivo, and a trend to decreased tumor tissue concentration of polyamines (spermidine). Indomethacin had no inhibitory effect on tumor cell proliferation in vitro, although PGE(2) production was decreased by 75%. The effect of indomethacin in vivo was independent of T-cells and was observed with similar magnitude irrespective of the number of MCG cells (10(4)-10(6)) implanted or the site of implantation (s.c., i.p., liver, lung, skeletal muscles). Tumor growth inhibition by indomethacin was not intrinsically transferable by tumor cells from indomethacin treated tumor-animals. Tumor expression of mRNA for several growth regulating factors were either increased (IL-6, TNF alpha, GM-CSF, TGF beta(3)) unchanged (EGF, VEGF, PDGF A,B, IL-1 alpha, transferrin receptor) or decreased (b-FGF and angiogenin) (p<0.05) by indomethacin treatment of MCG mice. Decreased tumor content of von Willebrandt factor VIII in combination with an attenuated tumor vasculature were associated with decreased tumor growth (p<0.05). Our results confirm that high tumor production of prostaglandins was related to reduced survival. Tumor prostaglandins probably promote local tumor growth by stimulation of tumor surrounding cells to produce growth factor(s) for tumor angiogenesis including tumor and matrix cell proliferation unrelated to immune cells.     

Prevention of peritoneal carcinomatosis recurrence with a prostaglandin synthesis inhibitor, indomethacin

Carcinomas produce large amounts of prostaglandin (PG) E2, which play an important role in suppression of non-specific cellular immune reaction in tumor-bearing individuals. PG synthesis inhibitor can restore the immune activity against tumors. The anti-tumor activity of indomethacin was investigated in CDF1 mice (BALB/c X DBA/2) implanted intraperitoneally with mouse colon adenocarcinoma 26 (5 X 10(5) or 2 X 10(5) cells) in a model study to prevent peritoneal recurrence after surgery for gastrointestinal cancers. Oral administration of indomethacin (0.002% water solution as drinking water) depressed and inhibited the disseminated tumor growth in the abdominal cavity, and prolonged the survival time, resulting in 30-50% cures of mice. The treatment combined with a small intraperitoneal dose of Picibanil (OK-432) (0.5 mg/kg twice weekly), which activates macrophages in the abdominal cavity, cured 90% of mice. An intraperitoneal dose of 16,16-dimethyl-PGE2 (5 micrograms/mouse, daily) reduced the anti-tumor activity of indomethacin. The results suggest that indomethacin treatment relieved the endogenous(tumor cell- and macrophage-produced) PGE2-mediated immunosuppression. It is postulated that PG-synthesis inhibitor in combination with chemotherapeutic agents, immunotherapeutic agents and low dose radiation, may provide a good therapeutic tool to prevent the development of peritoneal carcinomatosis, particularly in the cases having a small number of residual cancer cells or micrometastases in the abdominal cavity after surgery.     

Cross-talks in colon cancer between RAGE/AGEs axis and inflammation/immunotherapy

The tumour microenvironment is the result of the activity of many types of cells in various metabolic states, whose metabolites are shared between cells. This cellular complexity results in an availability profile of nutrients and reactive metabolites such as advanced glycation end products (AGE). The tumour microenvironment is not favourable to immune cells due to hypoxia and for the existence of significant competition between various types of cells for a limited nutrient pool. However, it is now known that cancer cells can influence the host''s immune reaction through the expression and secretion of numerous molecules. The microenvironment can therefore present itself in different patterns that contribute to shaping immune surveillance. Colorectal cancer (CRC) is one of the most important causes of death in cancer patients. Recently, immunotherapy has begun to give encouraging results in some groups of patients suffering from this neoplasm. The analysis of literature data shows that the RAGE (Receptor for advanced glycation end products) and its numerous ligands contribute to connect the energy metabolic pathway, which appears prevalently disconnected by mitochondrial running, with the immune reaction, conditioned by local microbiota and influencing tumour growth. Understanding how metabolism in cancer and immune cells shapes response and resistance to therapy, will provide novel potential strategies to increase both the number of tumour types treated by immunotherapy and the rate of immunotherapy response. The analysis of literature data shows that an immunotherapy approach based on the knowledge of RAGE and its ligands is not only possible, but also desirable in the treatment of CRC.     

Circulating human papillomavirus type 16 specific T-cells are associated with HLA Class I expression on tumor cells, but not related to the amount of viral oncogene transcripts

Human papillomavirus (HPV) is a necessary factor in the pathogenesis of cervical cancer. Circulating HPV-specific T-cells responding to the E6 and E7 HPV proteins can be detected only in half of cervical cancer patients. Potential explanations for the absence of this response are lack of sufficient amounts of antigen to activate the immune response or local immune escape mechanisms. We studied the relationship between HPV 16 E6/E7 oncogene mRNA expression, human leukocyte antigen (HLA) expression on tumor cells and the presence of circulating E6- and E7-specific T-cell responses in cervical cancer patients. The amount of antigen was assessed by HPV E6/E7 mRNA expression levels measured by quantitative polymerase chain reaction. HLA Class I and Class II expression on tumor cells was analyzed by immunohistochemistry. A proliferative HPV-specific T-cell response was detected in 15/29 patients. The amount of HPV E6/E7 mRNA was not related to the presence of immune response. HLA Class I expression was downregulated in 19 patients and completely lost in 7 patients. HLA Class II expression was upregulated in 18 patients. HLA Class I expression on tumor cells showed a strong correlation with immunity (p = 0.001). Explicitly, all patients with complete HLA loss lacked HPV specific T-cell responses. The presence of circulating HPV-specific T-cells might reflect ongoing antitumor response that is sustained by CD8+ T-cells killing HLA Class I positive cancer cells. We hypothesize that HLA Class I expression status on tumor cells might as well influence the response to HPV E6/E7 directed immunotherapy.     

Modulation of rat mammary carcinogenesis by indomethacin

Indomethacin, a nonsteroidal antiinflammatory agent which inhibits prostaglandin biosynthesis, has significant activity in inhibiting the growth and/or inducing the regression of transplantable tumors. The present study was designed to determine if, in addition to its chemotherapeutic effects, indomethacin also acts as a cancer chemopreventive agent. Fifty-day-old virgin female Sprague-Dawley rats were given a single intragastric dose of either 8 or 16 mg of 7,12-dimethylbenz(a)anthracene (time 0). Basal diet was supplemented with 25 or 50 mg of indomethacin per kg of diet by the following protocol: (a) -2 to +1 week; (b) +1 week to end; or (c) none. Administration of indomethacin by both protocols resulted in an inhibition of mammary tumorigenesis; however, the effect of -2 to +1 week indomethacin exposure was primarily on the induction of benign mammary tumors, while +1 week to end indomethacin administration inhibited the induction of both benign mammary tumors and mammary cancers. These data indicate that indomethacin has significant protective activity when administered either during the "early" stage (comprising the carcinogen-target cell interaction) or the "late" stage (postcarcinogen tumor development) of mammary carcinogenesis in rats. Possible mechanisms of indomethacin action include both local and systemic effects.     

The reversal of feline retroviral-induced suppression of lymphocyte Con A receptor mobility by indomethacin and PGE2

Ultraviolet light-inactivated feline leukemia virus (FeLV) and its 15,000 dalton envelope protein (p15E) inhibited concanavalin A receptor motility of feline peripheral lymphocytes (PBL). In contrast, the virus had no effect on immunoglobulin capping of feline PBL. The inhibitory action of FeLV and FeLV p15E was reversed by the addition of indomethacin. The indomethacin effect was titratable and gave significant reversal between 1 X 10(-5) and 1 X 10(-10) M. The indomethacin inhibition of the prostaglandin synthesis does not appear to be the mechanism of action in its ability to reverse FeLV suppression of Con A receptor mobility. Since the addition of prostaglandin E2 (PGE2) (1.0 microM) was also able to reverse the FeLV-induced inhibition and neither indomethacin nor PGE2 had an observable effect on Con A receptor mobility of normal PBL without FeLV present. PBL from FeLV-infected cats were sensitive to indomethacin (1.0-10.0 microM) and an indomethacin-related increase in cap formation was observed. Since both indomethacin and PGE2 were able to reverse the FeLV-induced suppression it was concluded that their mechanism of action may be through a common site. In addition, indomethacin may prove useful as an immune response modifier for therapy in FeLV-infected cats.     

The effect of an adjuvant mistletoe treatment programme in resected head and neck cancer patients: a randomised controlled clinical trial

The effect of an adjuvant mistletoe extract treatment was tested in a prospective, randomised controlled clinical trial involving 477 patients with head and neck squamous cell carcinoma. The patients were stratified into two treatment groups that underwent surgery or surgery followed by radiotherapy and both groups were randomised for additional treatment with mistletoe extract. Patients treated with a mistletoe lectin-1 (ML-1) standardised mistletoe preparation had no lower risk of local/locoregional recurrences, distant metastases or second primaries. In the main analysis based on 202 patients treated with surgery and 275 patients treated with surgery and radiotherapy the adjusted hazard ratio for the disease-free survival (DFS) was 0.959 (95% confidence interval (CI) 0.725-1.268). The 5-year survival rates of patients from the mistletoe group were no better than the survival rates of patients from the control group. Furthermore, no significant changes in the cellular immune reaction or in quality of life could be detected. We conclude that the used mistletoe preparation has no indication in the adjuvant treatment of patients with head and neck cancer.     

Immune blockade inhibitors and the radiation abscopal effect in gastrointestinal cancers

The field of tumor immunology has produced in the recent years a revolution in cancer therapeutics putting an end in the long lasting frustration of investigators in the area stemming from largely unsuccessful strides to develop cancer vaccines. This progress has come from the introduction of immune checkpoint inhibitors, monoclonal antibodies blocking ligand/receptor pairs with inhibitory effects for immune cells. Through this blockade immune checkpoint blockers are able to activate the immune system and create an anti-tumoral effect. A significant sub-set of patients with various types of cancers such as melanoma, lung carcinomas and urothelial cancers benefit from treatment with these drugs and survivals have improved in some cases. However other cancers are primarily resistant to immune blockers and secondary resistance is also the norm. Radiation therapy is often used in the palliative treatment of patients with advanced cancers and, in addition to the local effect in the irradiated field, it may in rare cases produce a systemic antitumor effect, termed “abscopal”. This effect has been suggested to be produced by immune mechanisms. Thus an opportunity presents for a synergistic effect of immune stimulation between radiation and immune blockade inhibitors. The therapeutic opportunities presented with the combination of radiation and these drugs for gastrointestinal cancers will be discussed in this editorial overview.     

Effects of KIR ligand incompatibility on clinical outcomes of umbilical cord blood transplantation without ATG for acute leukemia in complete remission

To clarify the effect of killer cell immunoglobulin-like receptor (KIR) ligand incompatibility on outcomes of acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) patients in complete remission after single cord blood transplantation (CBT), we assessed the outcomes of CBT registered in the Japan Society for Hematopoietic Cell Transplantation (JSHCT) database. A total of 643 acute leukemia (357 AML and 286 ALL) patient and donor pairs were categorized according to their KIR ligand incompatibility by determining whether or not they expressed HLA-C, Bw4 or A3/A11 by DNA typing. A total of 128 patient–donor pairs were KIR ligand-incompatible in the graft-versus-host (GVH) direction and 139 patient–donor pairs were incompatible in the host-versus-graft (HVG) direction. Univariate and multivariate analyses showed no significant differences between the KIR ligand-incompatible and compatible groups in the GVH direction for both AML and ALL patients of overall survival, disease-free survival, relapse incidence, non-relapse mortality and acute GVH disease. However, KIR incompatibility in the HVG direction ameliorated engraftment in ALL patients (hazard ratio 0.66, 95% confidence interval 0.47–0.91, P=0.013). Therefore, there were no effects of KIR ligand incompatibility in the GVH direction on single CBT outcomes for acute leukemia patients without anti-thymocyte globulin use. However, it is necessary to pay attention to KIR incompatibility in the HVG direction for engraftment.