776. Safety first
The distancing effect refers to the regression of radioactive field tumors during or after radiation therapy (RT), and has been reported in various cancers, such as melanoma, renal cell carcinoma and breast cancer. Although its mechanism has not been fully elucidated, the distancing effect may be mediated by enhanced systemic immune response induced by radiation. However, distancing effect is rarely observed, possibly due to the immune escape mechanisms of cancer cells, including activation of immune checkpoint pathways. In the past decade, newly developed immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment. With the emergence of ici which can enhance the systemic immune response to cancer cells, new treatment options combining ici and radiotherapy are expected to enhance the distancing effect. The synergistic effects of ici and RT �
Hepatocellular carcinoma (hcc) is the most common type of primary liver cancer and the second leading cause of cancer-related death worldwide. The overall survival rate of patients undergoing treatments such as resection, liver transplantation and ablation is >60%, while the advanced stage of chemoembolism or systemic treatment is poor. To improve this adverse outcome, new options have been added and suggested in the treatment, including the consideration of the use of ici. Therefore, various icis, including programmed cell death 1 �
(ctla- 4) Feasibility and safety in patients are being studied. However, the reported objective response rate (orr) of icis is only 15- 20%, which is still unsatisfactory. In addition, the recent evaluation of pembrolizumab treatment for patients with advanced hcc was not shown to be statistically significant in terms of improvements in overall survival and progression-free survival compared to placebo. Due to its immunogenic distancing phenomenon, rt has received considerable attention in terms of efficacy of ici
Efficacy in . However, the model, instead of using in situ model, can only observe the combined effect of rt
Hepa1-6
5, Figure 1c). The tumors harvested on day 31 (Figure 1d). Compared with a single 8 Gy irradiation, the total dose of 16 in two doses was significantly improved the survival rate of mice (p <0.001, Figure 1e). The total dose of 16 in the model was applied to the two doses of gy.
To determine whether local irradiation decreases in unirradiated tumor size is associated with immunogenic activation, we performed flow cytometry analysis of tumor-infiltrating lymphocytes (Figure 2a,b). The data showed that, rather than a single 8 Gy significantly increased cd4
.05 , Figure 2c) and unirradiated tumors (p<0.001 �
To understand how local irradiation shrinks unirradiated tumors, we used flow cytometry to detect DCS in the inguinal lymph nodes drained by tumors in the right hind leg of mice (Figure 3a,b). The data showed that the total dose of 16 Gy significantly increased the activated DCS ratio in TDLN
Total dose 16 Gy was induced in two irradiation (p <0.05, Figure 3c). In addition, the total dose 16 Gy significantly increased cd4 ifn-γ and cd8 ifn-γ
Based on the results of the expression of pd-l1 in tdln
(Not significant) growth. Compared with radiotherapy alone or anti-pd-1
Immunohistochemistry of specific antibodies using cd4 �
Flow cytometry analysis of tumors harvested on day 31 (Figure 5a) showed that in irradiated tumors, the total dose of 16 Gy was divided into two irradiation, rather than anti-pd-1
Irradiation increased the infiltration of total cd8 and cd8 ifn-γ T
Increased cd4 and cd4 in unirradiated tumors, but not cd8 cells, while their combined treatment increased total cd8 and cd8 cells more than any single treatment. Against
Compared with the treatment, the combination of radiation and anti-pd-1 antibody increased the infiltration of cd25 �
Flow cytometry immunophenotypic analysis showed that the number of cd220 b
The distancing effect is a rare phenomenon caused by radiation and can be enhanced by immunotherapy. Although radiation and immunotherapy are increasingly used to treat hepatocellular carcinoma (HCC), it is still unclear whether immunotherapy can enhance the distancing effect. In this study, the immunologic mechanism of the distancing effect caused by the combination of radiation and immunotherapy in the model. By inoculating mouse hepa1----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
The distribution of immune cells infiltrated with irradiated and unirradiated tumors and tumor drainage lymph nodes (tdln) was analyzed. Compared with a single 8gy irradiation, two total 16gy irradiation more effectively inhibited the growth of irradiated and unirradiated tumors, and the tumor infiltration of cytotoxic T cells was higher. The higher dose also increased activated dendritic cells in tdln, which had higher expression of programmed cell death ligand 1. The co-administration of anti-pd-1 antibodies significantly enhanced the dissociation effect and increased the infiltration of irradiated and non-irradiated activated cytotoxic T cells. The research results of irradiated tumors showed that the addition of anti-pd-1 in radiotherapy was performed in the homologous mouse model.
The production of red blood cells is a process that is strictly regulated. During the process of steady-state hemocytogenesis, the bone marrow produces about 1,010 red blood cells per hour to maintain hemoglobin levels within a very narrow range. In the case of continuous blood loss or hemolysis, the production of red blood cells can increase rapidly.
The erythrocyte progenitors of the bone marrow are directed differentiated single-line progenitor cells, which are randomly differentiated from progenitor cells with bidirectional or multidirectional differentiation potential (derived from a very small population of hematopoietic stem cells).
There are two types of erythroid progenitor cells [erythroidburst-forming unit, bfu-e) and erythroid colony-forming unit (cfu-e)] that cannot be identified by specific morphological characteristics, but can be purified and analyzed by flow cytometry. There is evidence that all hematopoietic progenitor cells or stem cells are similar to lymphoblasts.
1. Local irradiation reduces cell aggregation caused by tumors in mice's spleen
It was found that tumor-induced erythrocyte progenitor cells (epcs) production was significantly related to adverse prognosis, and targeting epcs or its products can inhibit tumor progression.
LCC tumor-bearing mice had spleen enlargement and basically returned to normal size after radiotherapy. After radiotherapy, the proportion also significantly returned to the baseline level. In addition, in the mc38, b16-siy, tumor-bearing model, a significant reduction in ter cells was also observed, indicating that the reduction in ter cells induced by radiotherapy is not limited to a certain tumor type.
2. Ifns �
? Literature reports that radiotherapy can trigger local and systemic anti-tumor immunity through type i interferon and T cells. In order to determine the role of type i ifnar-ko mice mediate ter cell reduction. Using ifnar-ko
?In view of the certain role of T cells in radiotherapy in anti-tumor, researchers explored the role of T cells in radiotherapy-mediated ter cell depletion. Using the immunodeficient mouse model, rag-ko, it was found that rag-ko, the ter cells did not decrease after radiotherapy in mice, indicating that radiotherapy-induced ter cell depletion is dependent on T cells.
?To explore the role of the cd4 or cd8 subpopulation T cells in it, after using antibodies to clear cd4 or cd8t cells, it was found that after clearing cd8t cells, the radiotherapy-induced ter
3. By blocking pd-l1, it can reduce tumor-induced cell aggregation that depends on cd8t cells and ifnγ.
? �
? pd-l1
4,ter �
?In vitro experiments found that co-culture of tumor cells with ter
?In in vivo models, anti-tumor effects of radiotherapy and pd-l1 are attenuated by adoptive transfer of ter cells or exogenous injections. It shows that the therapeutic effects of immunotherapy and radiotherapy depend in part on their inhibition of ter cells.
5. Destruction Destruction Axis can promote the efficacy of radiotherapy or io
?Destruction ter/artn Axis can improve the efficacy of radiotherapy and pd-l1 Anti-ter119 Anti-ter119 Absolutely depleted mice The effect of radiotherapy and pd-l1 The effect of antibodies is improved, and blocking artn The effect of radiotherapy and pd-l1 The effect of radiotherapy and pd-l1 The effect of radiotherapy and blocking �
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6. Radiotherapy and io response patients show treatment-induced cell reduction
?It was found that among the patients who received chemoradiotherapy, the concentration of artnnsclc in the blood of patients who did not relapse after treatment was significantly reduced after treatment, but there was no significant change in the blood of patients who relapsed after treatment.
A clinical trial found that patients undergo immunotherapy after radiotherapy, and the patient's cell abundance was significantly reduced after radiotherapy, and there was no significant change in cell abundance among patients with tumor progression (or non-responsive to treatment). It showed that the patient's response to radiotherapy and immunotherapy was related to their cell number and artn
?Research summary?
Chapter completed!