The emerging combination of radiation therapy with vaccines is a promising new treatment plan in the fight against cancer. While many cancer vaccines such as MUC1, p53 CpG oligodeoxynucleotide, and SOX2 may be great candidates for antitumor vaccination, there still remain many investigations to be done into possible vaccine combinations. One fruitful partnership that has emerged are anti-tumor vaccines in combination with radiation. Radiation therapy was previously thought to be only a tool for directly or indirectly damaging DNA and therefore causing cancer cell death. Now, with much preclinical and clinical data, radiation has taken on the role of an in situ vaccine. With both cancer vaccines and radiation at our disposal, more and more studies are looking to combining vaccine types such as toll-like receptors, viral components, dendritic-cell-based, and subunit vaccines with radiation. While the outcomes of these combinatory efforts are promising, there is still much work to be covered. This review sheds light on the current state of affairs in cancer vaccines and how radiation will bring its story into the future.

Cushman TR, et al. J Gynecol Oncol. 2018 Aug;29(6):e97. https://doi.org/10.3802/jgo.2018.29.e97

The triple therapy expresses high levels of TNF-α and IL-12 β cytokines. The NanoString results showed significant increase in IL-12 and TNF-α with the triple therapy group compared to no treatment. On the other hand, IL-6 was not significantly modulated.

Supplementary Figure S1. XRT (12 Gyx 2) with α-OX40 treatment effect on (A) tumor growth and (B) lung metastases in induction and adjuvant settings. (C) A representative picture depicting the decrease in lung tumor nodules with the combination therapy after staining with Bouin's fixative solution. /// Supplementary Figure S2. Effect of radiation (XRT) on immune-cell profiles in splenocytes (Spl) and draining lymph nodes (dLN). Representative flow cytometry gating of (CD4+OX40+) lymphocytes isolated from (A) spleen and (B) tumor draining lymph node of mice at 48 h after XRT (12 Gyx 3) or no XRT to anti-PD1 resistant tumors. /// Supplementary Figure S3. XRT upregulates OX40+ CD8 T-cells and enhances OX40L expression in neutrophils. (A) In anti-PD1-resistant 344SQ tumor model, XRT given as three 12-Gy fractions (total dose 36 Gy) increased the percentages of CD8+ T-cells expressing OX40 in the splenocytes 48 h after last dose of radiation. (B) Percent neutrophils expressing OX40L isolated from splenocytes 48 h after XRT. Cells are first gated on leukocytes then Gr1hi CD11b+ cells then on OX40L+ population. *P {less than or equal to} 0.05 is considered significant.

Purpose:Radiotherapy (RT) traditionally has been used for local tumor control in the treatment of cancer. The recent discovery that radiotherapy can have anticancer effects on the immune system has led to recognition of its ability to sensitize the tumor microenvironment to immunotherapy. However, radiation can also prompt adverse immunosuppressive effects that block aspects of systemic response at other tumor sites. Our hypothesis was that inhibition of the MER proto-oncogene tyrosine kinase (MerTK) in combination with anti-programmed cell death-1 (α-PD1) checkpoint blockade will enhance immune-mediated responses to radiotherapy.Experimental Design:We tested the efficacy of this triple therapy (Radiation + α-PD1 + α-MerTK mAbs) in 129Sv/Ev mice with bilateral lung adenocarcinoma xenografts. Primary tumors were treated with stereotactic radiotherapy (36 Gy in 3 12-Gy fractions), and tumors were monitored for response.Results:The triple therapy significantly delayed abscopal tumor growth, improved survival rates, and reduced numbers of lung metastases. We further found that the triple therapy increased the activated CD8+ and NK cells populations measured by granzyme B expression with upregulation of CD8+CD103+ tissue-resident memory cells (TRM) within the abscopal tumor microenvironment relative to radiation only.Conclusions:The addition of α-PD1 + α-MerTK mAbs to radiotherapy could alter the cell death to be more immunogenic and generate adaptive immune response via increasing the retention of TRM cells in the tumor islets of the abscopal tumors which was proven to play a major role in survival of non-small cell lung cancer patients.