Dr. Xueguan Lu with his team from Head and Neck Group of the Department of Radiation Oncology, Fudan University Shanghai Cancer Center (FUSCC) has lately reported new findings from a translational research on the characteristics of immune microenvironment in Human Papillomavirus (HPV)-positive oropharyngeal carcinoma. Based on single-cell RNA sequencing, flow cytometry, pharmaceutical inhibition and multiplex immunohistochemistry, his team reveals for the first time the existence of a specific CD161-positive cytotoxic T cell (CTL) subset featured by a seemingly exhausted phenotype but robust immune responses. In-depth analysis revealed that CD161+ CTLs exhibited a more robust anti-tumor effect over the CD161- cells and a T-cell inflamed phenotype that could be further reinvigorated by immune checkpoint blockade. Moreover, researchers found that high infiltration of CD161+ CTLs correlates with better treatment response and prolonged survival in HPV-positive oropharyngeal carcinoma. This study, which was published on AACR journal , might provide new insights into the prediction of treatment response and selection of therapeutic targets for HPV-positive oropharyngeal carcinoma in future.
HPV-positive oropharyngeal carcinoma is a unique head and neck with distinct biological behavior and clinical presentation. Despite the growing attention in western world during the past decade, this malignancy has been underestimated in China regarding its incidence and harm. According to data from FUSCC by Dr. Lu, HPV-positive patients account for approximately 60% in oropharyngeal carcinoma, which is approaching the figure in Europe and the USA. Although seen with better outcome when compared with its HPV-negative counterparts, HPV-positive oropharyngeal cancer is now endangering more people even in China with soaring incidence and a trend towards younger age, and thus bringing more challenges to the oncologists.
Dr. Xueguan Lu has been engaged since 2018 in the study of HPV-positive oropharyngeal cancer. When looking at its features of immune microenvironment, the team sorted out the special subset of CD161+ CTLs, which could be induced by E7 onco-peptides through HPV infection. Further analysis showed that these T cells are derived from naïve T cells that undergo a process of HPV-driven multi-differentiation. As CD161+ CTLs display both exhausted and active phenotypes, they would provide potential therapeutic biomarkers to target as their anti-tumor activity could be reinvigorated once the “immune brakes” such as PD-1or CD-39 are blocked by inhibitors. The researchers postulated that CD161+ CTLs actually represent the “inflamed” characteristics of HPV-positive oropharyngeal cancer, which might partly explain the favorable prognosis after treatment. This hypothesis was further testified through multiplex immunohistochemistry in oropharyngeal cancer tissues that were collected over years by the team.
It is alleged that the team of Dr. Lu has conducted multiple clinical and translational researches on HPV-positive oropharyngeal carcinoma, including the “IChoice” series of trials that focused on personal treatment de-intensification based on comprehensive chemoradiotherapy. Their findings have been selected for presentation in ASCO meeting 2022. Other investigations such as HPV DNA liquid biopsy, radiomics and transcriptomics for therapeutic prediction are also ongoing and more results are awaited in near future.