Cytokine evaluation in untreated and radioimmunotherapy-treated tumors in an immunocompetent rat model

Abstract

The tumor microenvironment can act so as to stimulate or reject tumor cells. Among the determining factors are cytokines produced, for example, by infiltrating immune cells, tumor cells, and fibroblasts. External radiotherapy has been shown to be able to activate an immune response against tumor cells with cytokine signaling as an important part of the activation. The aim of this study was to evaluate the cytokines present in the tumor microenvironment and whether the cytokine profile changed during tumor regression induced by radioimmunotherapy with the beta emitter 177 Lu. Immunocompetent rats with colon carcinoma tumors were injected with 400 MBq/kg 177 Lu-mAb, and the tumors were excised after 1, 2, 3, 4, 6, or 8 days post injection (4 rats/day on days 1-6 and 8 rats on day 8). Tumors from 10 untreated rats were used as control tissue. The tumors were divided into half: one half was prepared for cytokine analysis with a cytokine array kit and the other half was used for histological analysis. A total of 18 of the 29 cytokines evaluated were detected in this tumor model, and the majority of these act in a pro-inflammatory manner or stimulate the infiltration of immune cells. The differences between treated tumors and control tumors were small, thus the cytokine profile in the untreated tumors did not transfer to an anti-inflammatory profile during tumor regression induced by radioimmunotherapy with 177 Lu. Histological evaluation demonstrated a heterogeneous pattern of ongoing cell death and the formation of granulation tissue.

Size matters: Effect of granule size of the bone graft substitute (Herafill®) on bone healing using Masquelet's induced membrane in a critical size defect model in the rat's femur

“…This experiment was performed twice. Multiple publications are available using the kit successfully for the analysis of rat cytokines (Afroz et al, ; Cizkova et al, ; Elgström, Ohlsson, & Eriksson, ).…”

Therapeutic Irradiation: Consequences for Bone and Bone Marrow Adipose Tissue

“…Patients undergoing irradiation therapy have the potential to experience increased irradiation toxicity, even with fractionation of treatments, and adjacent soft tissue and bone damage as an adverse side effect due to limited tumor uptake and retention of irradiation doses (6). Tumor microenvironments promote tumor growth and angiogenesis through paracrine stimulatory factors and immune-mediated interactions (7). There are many cytokines released by the immune system that are considered “pro-tumor” or “anti-tumor” that alter the tumor microenvironment (7).…”

“…Tumor microenvironments promote tumor growth and angiogenesis through paracrine stimulatory factors and immune-mediated interactions (7). There are many cytokines released by the immune system that are considered “pro-tumor” or “anti-tumor” that alter the tumor microenvironment (7). After irradiation exposure, there are increased inflammatory cytokines, IL-1α/β, IL-6, IL-17, TNF-α, and VEGF, and evidence of increased cellular senescence, demonstrated through increased senescence-associated secretory phenotype (SASP) proteins (2, 7, 8).…”

“…There are many cytokines released by the immune system that are considered “pro-tumor” or “anti-tumor” that alter the tumor microenvironment (7). After irradiation exposure, there are increased inflammatory cytokines, IL-1α/β, IL-6, IL-17, TNF-α, and VEGF, and evidence of increased cellular senescence, demonstrated through increased senescence-associated secretory phenotype (SASP) proteins (2, 7, 8). This change to the tumor microenvironment and increased immune activity is thought to explain the abscopal effect, in which localized irradiation results in regression of metastatic cancer that are distant from the initial irradiation site (7).…”

Monocyte programming by cancer therapy

“…Local tissue destruction has more pronounced extend compared to the systemic one. After irradiation, the production of cytokines IL-1α/β, IL-6, IL-17, TNF-α, and VEGF is increased, and cellular senescence in a blood is levated ( Figure 1B ) ( 109 – 111 ). Below we present accumulated data about the effect of irradiation on monocyte biology in peripheral blood and tissues.…”