Radiation and Synergy with Immunotherapy – Bone metastisis

Interesting that this relationship has been known about since at least 2008.

http://www.cancernetwork.com/end-life-care/synergizing-radiation-therapy-and-immunotherapy-curing-incurable-cancers/page/0/2

Excerpt:   "

Reduction to Practice: Preclinical Studies

External-Beam Radiation and Cancer Immunotherapy

In vivo preclinical studies have demonstrated that the combination of tumor-focused external-beam radiation and immunotherapy can facilitate antitumor immunity better than either modality alone. Younes et al[24] studied endogenous T-cell responses to renal cell carcinoma with bilateral pulmonary metastases in a murine model and observed that local irradiation to the left lung in combination with systemic IL-2 (Proleukin) therapy led to greater tumor reduction in both lungs than was achieved by either modality alone.

For active specific immunotherapy, therapeutic cancer vaccines are being investigated. TAAs such as CEA and MUC-1, which are overexpressed on a wide variety of tumor cells in vivo,[25] are being studied as targets for vaccine-mediated immunotherapies.[26-29] Chakraborty et al[30] have focused on the combination of low-dose radiation (8 Gy) delivered directly to the tumor, and active therapeutic vaccination for the treatment of subcutaneous murine tumors. There, the vaccine was composed of poxviral vectors that express CEA and three T-cell costimulatory molecules: B7-1, ICAM-1, and LFA-3 (CEA/TRICOM). Although either modality alone was ineffective, the combination of radiation and vaccine was not only curative in 50% of mice bearing CEA-expressing tumors, but also imparted protection from subsequent tumor challenge.

Interestingly, mice cured of tumors demonstrated “antigen cascade”; that is, they developed CD4-positive and CD8-positive T-cell responses not only for CEA, but also for other tumor antigens not encoded in the vaccine, such as p53 and gp70. The immune response to gp70 was much greater than that seen to the vaccine-encoded CEA, suggesting that the immune response to the cascade antigen may play an important role in antitumor activity. This antigen cascade phenomenon has also been observed in patients enrolled in clinical trials (see below).

Bone-Seeking Radionuclide and Cancer Immunotherapy

In advanced stages, many primary human carcinomas such as thyroid, breast, kidney, prostate, and multiple myeloma typically involve painful bone metastases that require palliative therapy. Strontium-89 (89Sr, Metastron) and samarium-153 (153Sm lexidronam, Quadramet) are bone-seeking radiopharmaceuticals used to relieve the pain of metastasis to bone. The calculated dose of palliative radiation delivered to bone metastases by 153Sm lexidronam is between 18 and 80 Gy[31,32]—doses that have been associated with phenotypic modulation of human tumor cells.

In one study, 10 human tumor-cell lines representing classes of tumors that metastasize to bone (4 prostate, 2 breast, and 4 lung) were exposed to clinically relevant palliative levels of 153Sm lexidronam for 4 days, then examined by flow cytometry for modulation of several cell-surface molecules. Of the 10 cell lines, 100% upregulated Fas and CEA, 70% upregulated MUC-1, 40% upregulated MHC class I, and 30% upregulated ICAM-1. Upregulation of any of these surface molecules could potentially render tumor cells more susceptible to killing by CTLs.[33]