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The application of immune checkpoint inhibitors (ICI) has rewritten the current treatment pattern of non-small cell lung cancer. However, single-agent ICI has disadvantages such as small benefit population and slow tumor cytoreduction effect. Therefore, various immunizations combined with other treatment methods are becoming clinical hotspots. Low-dose irradiation shows a significant anti-tumor synergistic effect through activating the body's immune system, and its potential for adjuvant immunotherapy has transformed traditional radiotherapy from local radical treatment to immune adjuvant. This article reviews the current research progress of ICI combined with low-dose irradiation in the treatment of non-small cell lung cancer.
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Objective To investigate the effect of whole-body irradiation with low-dose γ-rays on the central nervous system of mice.Methods Fifty C57 mice were randomly divided into 3 groups and treated with 0,0.5,1 Gy whole-body irradiation,respectively.24 or 48 h after irradiation,brain tissue of mice was resected and homogenated.The levels of amino acid neurotransmitter,including Glu,Asp,GABA and Gly in brain homogenate were measured by high performance liquid chromatography (HPLC).Results Compared to the brain tissue of untreated mice,the contents of Glu and Asp at 0.5 and 1 Gy (t=-4.080,-3.935,-4.416,-3.630,-4.831, - 4.656,P ＜0.05) in mice brain tissue significantly increased at 24 h at 1 Gy and 48 h.However,the contents of Glu and Asp had no obvious changes in mice brain tissue 24 h after 1 Gy of irradiation. The contents of GABA and Gly had no difference between irradiated groups and untreated control group. Conclusions Short-term whole-body irradiation with low-dose γ-rays induces slight stimulation effect on the central nervous system of mice.
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Objective To observe the effects of low dose irradiation (LDR) on proliferation,adipogenesis and osteogenic potential of human umbilical cord mesenchymal stem cells (hucMSCs).Methods hucMSCs were isolated from Wharton's jelly tissue of human umbilical cord by modified tissuepiece inoculation,and flow cytometry was used to detect the expression of specific marker in the hucMSCs.The hucMSCs were randomly divided into two groups:irradiation group undergoing irradiation with the doses 50,100,or 200 mGy respectively,and control group without irradiation.MTT method was applied to evaluate the proliferation of the hucMSCs at different time points with various doses irradiation.The third passage hucMSCs were randomly divided into two groups:irradiation group undergoing low dose irradiation of 200 mGy,and control group without irradiation,and then underwent induction by adipocytic and oesteocytic differentiation induction fluids respectively so as to differentiate into adipocytes and osteoblasts.Oil red O staining was used to detect the activity of alkaline phophatase (ALP),and RT-PCR was used to detect the mRNA expression of core binding factor alpha 1 in human osteoblast.Results After 9-12days,fibroblasts began to swim out of the tissue piece with a confluence rate of 80% 2 weeks later.Within 7 days the absorption values of the hucMSCs undergoing different irradiation doses 2,3,4,5,and 6 days later were all significantly higher than those of the control group(F = 159.17,448.81,265.15,183.93,and 181.83 ,all P <0.01),with the proliferation rates of the 100 mGy subgroup being the highest.After being induced liquid,vacuoles were observed in the irradiated group 2 days later.21 days later,the adipogenic rates of irradiated group was significantly higher than that of the control group (t = 28.25,P <0.01).The ALP activity increased in the irradiated group compared with control group (t=16.87,P <0.01) .The expression level of Cbf-α1 mRNA was up-regulated obviously (t = 14.16,P＜0.01).Conclusions LDR promotes the proliferation of hucMSCs,and accelerates the hucMSCs' differentiation into adipocytes and osteoblasts.
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Objective To observe the effects of low dose irradiation (LDI) on autoiogous CIK cell proliferation, phenotype and killing activity in tumor patients, and to provide the evidence for clinical application of adoptive immunotherapy with CIK cells. Methods Peripheral blood mononuclear cells (PBMC) were separated from 10 patients with malignant tumor, and CIK cells were cultured with different cytokines. (1) After 10 d culture, C1K cells were irradiated with different doses as 30, 50, 80, 100 and 200 Gy of X-rays was also detected. The CIK cell proliferation and killing activity were measured with 3H-TdR incorporation assay and 3H-TdR release assay, respectively and the percentage variation of CD3 +CD56 + were measured with flow cytometry after 24 h. ( 1 ) Autologous CIK cells were irradiated with 80 mGy X-rays. At different culture time ( 12, 24, 48, 72 h) after irradiation, the killing activity was measured with 3H-TdR release assay. (3) The effect of 3d low dose irradiation of 80 mGy X-rays on thekilling activity of CIK cells was also detected. Results After the CIK cells were irradiated with different doses as 50, 80, 100, 200 mGy of X-rays, the CPM values were 20 048.6 ± 2332. 2 ( t = 2.2, P ＜0.05), 21 832.2 ±2975.9 (t=3.5, P＜0.01), 21 000.3 ±2451.1 (t=3.3, P＜0.01), 19908.1 ±2051.0 ( t = 2.2, P ＜ 0.05 ), respectively and the proliferation of CIK cells were significantly higher than that of control group. The CD3 + CD56 + cell percentage of 50, 80, 100 mGy groups were ( 30.3 ±3.8)% (t=2.3, P＜0.05), (32.3±3.4)% (t=4.2, P＜0.01), (29.742.9)% (t = 2.4, P＜0.05 ), respectively. The killing activity of CIK cells of 80, 100 mGy groups were 55.2 ± 5.0 ( t = 3.3, P ＜ 0.01 ), 52.8 ± 4.1 ( t = 2.3, P ＜ 0.05 ), respectively. The killing activity of CIK cells up-regulated significantly at 24 h, dropped to normal levels at 48 h and 72 h. After 80 mGy X-ray irradiation for 3 consecutive days, the killing activity of CIK cells at different time points were 55.2 ± 5.3 (t = 2.6, P ＜0.05),61.9 ± 4.4 (t = 4.7, P ＜0.01), 67.2 ±5.7 (t = 5.7, P ＜0.01) for 24, 48, 72 h,respectively. Conclusions LDI might have the hormesis effect on CIK cells.
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Objective To study the expression of membrane molecules of T lymphocytes of cord blood after low dose irradiation(LDI). Methods Freshly isolated lymphocytes from cord blood were irradiated with 62mGy gamma-ray. At different time(4h; 12h;24h) after irradiation, the changes of TCR+, CD3 +, CD4 +, CD8 + cells were examined by flow cytometry with direct immunofluorescence, respectively. Results The proportion of CD3 +, TCR+ /CD3 +; CD4 +, CD8 + cells increased significantly after LDI,the most obvious enhancement was noted in the 24h experimental group were no significant changes in the ratio of CD4 to CD8. Conclusions It is suggested that expedition of the maturation, activation and signal transudation of T lymphocytes from cord blood can be induced by ir- radiation with 62mGy gamma-ray The reconstruction of immune functions after cord blood transplantation may be ac- celerated, enhancing the graft versus leukemia(GVL)effect and preventing the tumor from relapsing.