Cancer immunity and therapy using hyperthermia with immunotherapy, radiotherapy, chemotherapy, and surgery

Yagawa, Yohsuke; Tanigawa, Keishi; Kobayashi, Yuki; Yamamoto, Masakazu

doi:10.20517/2394-4722.2017.35

Cited by 96 publications

(65 citation statements)

References 101 publications

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“…Thus, confirmation of either of these hypotheses and further investigation, for example, using histological analysis, is required. Although an increase in growth rate of heated spheroids may seem to contradict the use of hyperthermia, it should be stressed that the in vitro spheroid culture does not account for other potential beneficial physiological effects of this treatment in vivo, such as immune stimulation 46,47 . Moreover, re-oxygenation and active proliferation of previously quiescent cell populations sensitises these to fractionated radiation treatments and it would thus be essential to further investigate the efficacy of fractionated treatments which could indeed show a further benefit of combined RTHT treatments despite an enhanced growth of spheroids following a single treatment fraction.…”

Section: Discussionmentioning

confidence: 99%

3D tumour spheroids for the prediction of the effects of radiation and hyperthermia treatments

Brüningk

Rivens

Box

et al. 2020

Sci Rep

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Carol Box , Uwe oelfke & Gail ter Haar For multimodality therapies such as the combination of hyperthermia and radiation, quantification of biological effects is key for dose prescription and response prediction. Tumour spheroids have a microenvironment that more closely resembles that of tumours in vivo and may thus be a superior in vitro cancer model than monolayer cultures. Here, the response of tumour spheroids formed from two established human cancer cell lines (HCT116 and CAL27) to single and combination treatments of radiation (0-20 Gy), and hyperthermia at 47 °C (0-780 CEM 43) has been evaluated. Response was analysed in terms of spheroid growth, cell viability and the distribution of live/dead cells. Time-lapse imaging was used to evaluate mechanisms of cell death and cell detachment. It was found that sensitivity to heat in spheroids was significantly less than that seen in monolayer cultures. Spheroids showed different patterns of shrinkage and regrowth when exposed to heat or radiation: heated spheroids shed dead cells within four days of heating and displayed faster growth post-exposure than samples that received radiation or no treatment. Irradiated spheroids maintained a dense structure and exhibited a longer growth delay than spheroids receiving hyperthermia or combination treatment at (thermal) doses that yielded equivalent levels of clonogenic cell survival. We suggest that, unlike radiation, which kills dividing cells, hyperthermia-induced cell death affects cells independent of their proliferation status. This induces microenvironmental changes that promote spheroid growth. In conclusion, 3D tumour spheroid growth studies reveal differences in response to heat and/or radiation that were not apparent in 2D clonogenic assays but that may significantly influence treatment efficacy. Whilst monolayer cell cultures have underpinned decades of cancer research, they have been criticized for not being reliable predictors of treatment response in vivo 1,2. The culture geometry of a flat, rigid substrate limits the number of neighbouring cells, resulting in reduced inter-cellular contact and communication compared with cells in vivo. Two dimensional (2D) culture conditions cause cells to stretch, increasing the surface area directly exposed to culture medium 3-5. Cancer cells cultured in 2D are thus always provided with oxygen and nutrients. These are more restricted in the physiological microenvironment of a tumour where inefficient vasculature prevents their homogeneous supply. Despite these limitations, advantages such as low cost, high throughput, ease of application and control over microenvironmental factors have made monolayer cultures the standard technique for evaluation of cellular responses. However, there may be considerable inconsistencies between experimental results obtained in vitro in 2D culture and those observed in vivo. One possible way of bridging this gap is to use three dimensional (3D) tumour spheroid cultures. Here, cells are grown as aggregates of single or multiple cell types, ...

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Section: Discussionmentioning

confidence: 99%

3D tumour spheroids for the prediction of the effects of radiation and hyperthermia treatments

Brüningk

Rivens

Box

et al. 2020

Sci Rep

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“…Several experimental studies have shown that rise in body temperature activates immune system which contribute to protect against infection and cancer [5][6][7][8] Two limitations of our study should be addressed. First, the study population was limited in number.…”

Section: Discussionmentioning

confidence: 95%

“…Body temperature is one of the major physiological parameter related to health condition, which differs by age and elderly has lower body temperature compared to young adults [1]. Decrease in body energy expenditure, skeletal muscle mass and physical activity in the elderly attenuate to lower body temperature [2][3][4], which contribute to inactivate immune function against infection and cancer [5][6][7][8][9]. Exercise training, including aerobic and anaerobic, is effective to increase body energy expenditure and skeletal muscle mass.…”

Section: Introductionmentioning

confidence: 99%

Effect of exercise training on body temperature in the elderly: a retrospective cohort study

Matsumura

Iwasaka

Mizuno

et al. 2020

Preprint

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Background Although rise in body temperature in the elderly has clinical benefits such as activating immune system, little is known regarding the mediator related to the elevation of body temperature. This study evaluated the effect of exercise training on body temperature and clarified the relationship between body temperature and body composition in the elderly. Methods In this retrospective cohort study, a total of 91 elderly participants performed aerobic and anaerobic exercise training twice a week for 2-year. Non-contact infrared thermometer and bioelectrical impedance analysis were performed at baseline and at 2-year. The participants were divided into 2 groups by baseline body temperature of 36.3℃; lower body temperature group (n = 67) and normal body temperature group (n = 24). Results Body temperature rose significantly after exercise training (36.04 ± 0.01 °C to 36.30 ± 0.02 °C, p < 0.0001) in the lower body temperature group, whereas there was no significant difference (36.35 ± 0.02 °C to 36.36 ± 0.03 °C, p = 0.39) in the normal body temperature group. A positive correlation was observed between the amount of change in body temperature and baseline body temperature (r = -0.68, p < 0.0001). Increase in skeletal muscle mass was an independent variable related to the rise in body temperature by the multivariate logistic regression analysis (odds ratio: 4.77, 95% confidence interval: 1.29–17.70, p = 0.02). Conclusions Exercise training raised body temperature in the elderly, especially those with lower baseline body temperature.

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“…HT is known to induce vasodilation, which allows for infiltration of immune cells. Additionally, hyperthermia increases immunogenic surface receptors such as NKG2D and ligand-like MHC-I and it promotes expression of heat-shock proteins (HSP) for enhanced antigen presentation [17][18][19]. Though RT and hyperthermia exert pro-immune effects on the TME, those responses can likely be further directly enhanced with immune stimulation using immunotherapy agents.…”

Section: Introductionmentioning

confidence: 99%

A Combination of Radiotherapy, Hyperthermia, and Immunotherapy Inhibits Pancreatic Tumor Growth and Prolongs the Survival of Mice

Mahmood

Alexander

Samanta

et al. 2020

Cancers

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Background: Pancreatic cancer (PC) is the fourth-most-deadly cancer in the United States with a 5-year survival rate of only 8%. Unfortunately, only 10–20% of PC patients are candidates for surgery, with the vast majority of patients with locally-advanced disease undergoing chemotherapy and/or radiation therapy (RT). Current treatments are clearly inadequate and novel strategies are crucially required. We investigated a novel tripartite treatment (combination of tumor targeted hyperthermia (HT), radiation therapy (RT), and immunotherapy (IT)) to alter immunosuppressive PC-tumor microenvironment (TME). (2). Methods: In a syngeneic PC murine tumor model, HT was delivered before tumor-targeted RT, by a small animal radiation research platform (SARRP) followed by intraperitoneal injections of cytotoxic T-cell agonist antibody against OX40 (also known as CD134 or Tumor necrosis factor receptor superfamily member 4; TNFRSF4) that can promote T-effector cell activation and inhibit T-regulatory (T-reg) function. (3). Results: Tripartite treatment demonstrated significant inhibition of tumor growth (p < 0.01) up to 45 days post-treatment with an increased survival rate compared to any monotherapy. Flow cytometric analysis showed a significant increase (p < 0.01) in cytotoxic CD8 and CD4+ T-cells in the TME of the tripartite treatment groups. There was no tripartite-treatment-related toxicity observed in mice. (4). Conclusions: Tripartite treatment could be a novel therapeutic option for PC patients.

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Cancer immunity and therapy using hyperthermia with immunotherapy, radiotherapy, chemotherapy, and surgery

Cited by 96 publications

References 101 publications

3D tumour spheroids for the prediction of the effects of radiation and hyperthermia treatments

3D tumour spheroids for the prediction of the effects of radiation and hyperthermia treatments

Effect of exercise training on body temperature in the elderly: a retrospective cohort study

A Combination of Radiotherapy, Hyperthermia, and Immunotherapy Inhibits Pancreatic Tumor Growth and Prolongs the Survival of Mice

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