Guest blog from Colin Ruggerio.
Arya Stark braved Daenerys’ attack on Kings Landing and survived, but she’s not out of the woods for developing a serious respiratory-related illness. Both during and after Khaleesi’s dragon attack, we’re presented with images of Arya running through ash, smoke, and debris, all of which could have contained harmful toxicants released by Drogon’s scorching flames. One of the most harmful carcinogens she could have encountered is asbestos (who knows what King’s landing is built with and surprisingly in some countries in this world, asbestos is still used). When inhaled, asbestos fibers may become lodged in the lining of the internal organs, where they irritate tissue and cause the development of tumors1. Over the next 10 to 50 years, Arya may slowly begin to uncover symptoms of mesothelioma cancer, an aggressive disease that primarily affects the pleural cavity and can’t be solved with a Valyrian steel dagger.
For mesothelioma patients, treatment options are limited and survival rate is between 4 to 18 months. However, new forms of treatment, such as immunotherapy are emerging. Immunotherapy utilizes the body’s own immune system to destroy cancer cells. Studies of patients with mesothelioma are attempting to discern if tumors affect the CD4:CD8 cell ratio in the blood as well as whether the immune response in the tumor is skewed. For Arya, she may be in luck depending on what her CD4:CD8 ratio looks like.
In a recent study, a cohort of 302 formalin-fixed paraffin-embedded samples from patients with mesothelioma were analyzed. Tissue Microarrays (TMAs) were examined for populations of CD8+, FOXP3+, CD4+, CD45RO+, CD3+ T-cells and CD20+ B-cells.2 Of the 302 patient samples that were examined, 259 underwent palliative care, 7 underwent an image-guided pleural biopsy, and 36 underwent an intensive surgical procedure, such as a pleuro-pneumonectomy. Results broke down these 302 samples into further divisions to understand the correlation between tumor type and cell presence. The tumor types that were present among the 302 samples were as follows: 172 epithelioid, 82 biphasic, 41 sarcomatoid, and 7 undefined. The median overall survival rate for epithelioid mesothelioma was 342 days and non-epithelioid mesothelioma median overall survival rate was 205 days.2
Among the epithelioid tumor samples, high CD4+ (P=0.005), high CD20+ (P=0.024), and low FOXP3+ (P=0.008) cell counts were noted to show a better outcome, with a longer overall survival of 7, 3, and 7 months respectively, compared to low CD4+, high FOXP3+, and low CD20+ cells.2 In the non-epithelioid tumor samples, low CD8+ and low FOXP3+ showed an overall survival of 4 months longer than the grouping of high CD8+ and high FOXP3+ cells.
Overall, findings from this study found that high CD8+ presence did not have an effect on the overall survival of the epithelioid group, and the non-epithelioid group actually was noted to have greater survival advantage with a low presence of CD8+ T-cells.2 As for CD4+ presence, a high density of this T-cell was found to create a survival advantage for the epithelioid group. Of the entire cohort, research found that a CD4+:CD8+ ratio greater than 1 showed better survival in the epithelioid group.2
Further research must be completed to better understand how immunotherapy can work based on certain cell densities. For Arya, if she does in fact develop mesothelioma cancer, it seems that her cell densities will play a role in her prognosis but hopefully, by then an immunotherapy will be foolproof against this deadly disease.
For more information on mesothelioma cancer, visit mesothelioma.com/mesothelioma.
1 https://www.mesothelioma.com/asbestos-exposure/what-is-asbestos/. Accessed 9/10/19.
2. Chee, Serena J et al. “Evaluating the effect of immune cells on the outcome of patients with mesothelioma.” British journal of cancer vol. 117,9 (2017): 1341-1348. doi:10.1038/bjc.2017.269