Intraoperative radiation therapy induces immune response activity after pancreatic surgery.

BACKGROUND: Pancreatic cancer has highly aggressive features, such as local recurrence that leads to significantly high morbidity and mortality and recurrence after successful tumour resection. Intraoperative radiation therapy (IORT), which delivers targeted radiation to a tumour bed, is known to reduce local recurrence by directly killing tumour cells and modifying the tumour microenvironment. METHODS: Among 30 patients diagnosed with pancreatic cancer, 17 patients received IORT immediately after surgical resection. We investigated changes in the immune response induced by IORT by analysing the peritoneal fluid (PF) and blood of patients with and without IORT treatment after pancreatic cancer surgery. Further, we treated three pancreatic cell lines with PF to observe proliferation and activity changes. RESULTS: Levels of cytokines involved in the PI3K/SMAD pathway were increased in the PF of IORT-treated patients. Moreover, IORT-treated PF inhibited the growth, migration, and invasiveness of pancreatic cancer cells. Changes in lymphocyte populations in the blood of IORT-treated patients indicated an increased immune response. CONCLUSIONS: Based on the characterisation and quantification of immune cells in the blood and cytokine levels in the PF, we conclude that IORT induced an anti-tumour effect by activating the immune response, which may prevent pancreatic cancer recurrence. CLINICAL TRIAL REGISTRATION: NCT03273374 .

Effects of peritoneal lavage fluid from radiation or/and burn injured rats on the growth of hematopoietic progenitor cells.

PURPOSE: To evaluate the effects of peritoneal lavage fluids from radiation injury, burn injury and combined radiation-burn injury on the growth of hematopoietic progenitor cells (HPC). MATERIALS AND METHODS: Rats were divided into four groups: A radiation group (RG), a burn group (BG), a combined radiation-burn group (CRBG) and normal control group (NG). RG and CRBG rats were irradiated with 12 Gy, and burns of 30% total body surface area were generated in group BG and group CRBG. Peritoneal lavage fluids were collected and tested for their effects on the growth of erythrocyte progenitor cells or granulocyte-macrophage progenitor cells of BALB/c mice in vitro. RESULTS: The numbers of colony forming units-erythroid (CFU-E), burst forming units-erythroid (BFU-E) and colony-forming units-granulocyte-macrophage (CFU-GM) formed after treatment with lavage fluids from BG or CRBG were significantly higher than those from NG. However, fewer CFU-E, BFU-E or CFU-GM colonies were found after treatment with lavage fluid from the RG. In lavage fluid from BG and CRBG, the concentration of interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor alpha (TNFalpha) was increased in comparison to NG and RG. Treatment with these cytokines had similar promoting effects on the growth of hematopoietic colonies and neutralizing antibodies inhibited these effects significantly. CONCLUSIONS: Burns increase the responsiveness of the system and help the proliferation of hematipoietic progenitor cells, while radiation decreases all these responses relative to both the controls and the burn plus radiation group.

Regulation of macrophage populations. III. The immunologic induction of exudates rich in Ia-bearing macrophages is a radiosensitive process.

We have evaluated some of the conditions regulating the selective augmentation of the Ia-positive macrophage population within immunologically induced exudates. Antigen-stimulated T cells secrete a protein referred to as macrophage- (Ia-positive) recruiting factor (MIRF), which when injected i.p. stimulates a 10- to 20-fold increase in the number of Ia-positive exudate macrophages. This response is totally abrogated when mice are lethally irradiated before injection of MIRF or immune T cells. Adoptive transfer of bone marrow cells to irradiated mice substantially restores their ability to respond to the immunologic stimuli, even if the transferred bone marrow has itself been depleted of Ia-positive cells. It was also found that the high level of Ia-positive macrophages induced by MIRF requires a renewable stem cell source in order to be maintained. Finally, even when macrophages were elicited by injecting thioglycollate before irradiation, Ia-positive cells were not induced in response to MIRF. These findings suggest that the target of MIRF in vivo may be restricted to a developmentally young cell within or recently derived from a stem cell compartment such as the bone marrow, and that Ia-positive and Ia-negative macrophages ultimately derive from a potentially common Ia-negative stem cell.

A direct macrophage migration inhibition test applied in man.

A direct macrophage migration test is described, which proved to be useful for the detection of cellular hypersensitivity in man. We used a modification of the method described by Hughes & Paty (1972). In this method the MLR is abolished by 100 rad gamma-irradiation of the peritoneal exudate cells prior to pooling with human lymphocytes. Experiments with various intensity of irradiation, PPD, muscle antigen and encephalitogenic factor were performed to check this method. In a pilot study lymphocytes of patients with diseases of the central or peripheral nervous system or of muscle were tested. This proved that a hypersensitivity of Ef was present in various diseases of the CNS, while in muscle diseases positive tests were found using muscle antigen.

Spontaneous conversion of precursor cells into cells producing antibodies against sheep erythrocytes in cultures of mouse peritoneal cells.

The role of cell division in the spontaneous development of antisheep PFC in cultures of mouse peritoneal cells has been studied. Mitotic index measurement showed that most PFC were not recruited by division. LPS (a blastogenic and mitogenic substance) increased the number of PFC much more than it increased the number of mitosis. X-ray-irradiation of the donor mice did not affect the kinetics of PFC development. It was, therefore, concluded that PFC recruitment in mouse PC in culture was essentially related to cell differentiation, cell division playing only a minor role.

Interferon synthesis in mouse peritoneal cells damaged by X-irradiation.

NDV-induced interferon of peritoneal cells of irradiated (X-rays, 400 R) and control mice was investigated in vitro. Irradiation or treatment with hydroxyurea (10(-5) M) and mitomycin C (25 microng/ml) did not change interferon synthesis in spite of an 80--90% inhibition of 3H-thymidine incorporation. Increased doses of mitomycin C and treatment with actinomycin D and puromycin blocked interferon production. De novo interferon synthesis occurred in cells with damaged replicative activity of DNA caused by irradiation or by treatment with antimetabolites.