Radiotherapy and the Tumor Stroma: The Importance of Dose and Fractionation

Abstract

Ionizing radiation is a non-specific but highly effective way to kill malignant cells. However, tumor recurrence sustained by a minor fraction of surviving tumor cells is a commonplace phenomenon caused by the activation of both cancer cell intrinsic resistance mechanisms, and also extrinsic intermediaries of therapy resistance, represented by non-malignant cells and structural components of the tumor stroma. The improved accuracy offered by advanced radiotherapy (RT)-technology permits reduced volume of healthy tissue in the irradiated field, and has been triggering an increase in the prescription of high-dose oligofractionated regimens in the clinics. Given the remarkable clinical success of high-dose RT and the current therapeutic shift occurring in the field, in this review we revise the existing knowledge on the effects that different radiation regimens exert on the different compartments of the tumor microenvironment, and highlight the importance of anti-tumor immunity and other tumor cell extrinsic mechanisms influencing therapeutic responses to high-dose radiation.

Chemotherapeutic tumor microparticles combining low-dose irradiation reprogram tumor-promoting macrophages through a tumor-repopulating cell-curtailing pathway

“…To decrease the side effects, low-dose irradiation (LDI) has been explored. Intriguingly, despite its very poor tumor cell-killing effect, LDI is actually able to improve antitumor immunity through modulating macrophages, recruiting T cells to tumor sites and other ways, [19][20] raising a possibility of LDI enhancing the anti-TRC effect of drug-MPs followed by a better modulation of antitumor immune microenvironments. This study demonstrates that the combination of drug-packaging MPs and LDI effectively reverses macrophage polarization from tumor-promoting to tumor-inhibiting through disrupting TRCs, providing a new strategy for tumor immunotherapy.…”

Volumetric‐based image guidance is superior to marker‐based alignments for stereotactic body radiotherapy of prostate cancer

“…Several recent SBRT studies showed local control rates and toxicity profiles were comparable to the conventional dose regimen of 2 Gy per fraction (2 Gy/Fx) 2, 3. It has been reported that with a prescription dose of 7.25 Gy/Fx or higher in SBRT treatment planning, margins are usually 5 mm or smaller to spare the surrounding organs at risk such as rectum, urethra, and bladder 1.…”

Peripheral myeloid-derived suppressor and t-regulatory pd-1 positive cells predict response to neoadjuvant short-course radiotherapy in rectal cancer patients

“…Through an active humoral and physical cross talk ME can determine invasion, ability to metastasize, immunogenicity of cancer and response to anticancer therapies including radiation therapy (RT). The effects of radiotherapy reported on tumor cells are conflicting, and the general belief on immunity is that different microenvironments and diverse delivery modalities may induce activation or inhibition of immune response and the size of fraction is one of the variables involved in such a dualism [1][2][3].…”