Tumour infiltrating lymphocytes in oropharyngeal carcinoma: prognostic value and evaluation of a standardised method.

Tumour infiltrating lymphocytes (TILs) have been described as a biomarker for the host immune response against the tumour with prognostic properties. The International Immuno-Oncology Biomarkers Working Group (IBWG) proposed a standardised method for quantifying TILs in solid tumours to improve consistent and reproducible scoring. In this study, the methodology was tested in a retrospective population of oropharyngeal squamous cell carcinoma (OPSCC). TIL quantification was performed on 92 OPSCC samples (2004-2013) by four independent observers as described by the IBWG. Interobserver variability was assessed and results were correlated with clinicopathological variables and survival. TIL evaluation turned out to be challenging in OPSCC due to heterogeneity of TILs distribution, presence of pre-existing lymphoid tissue, surface ulceration or erosion and insufficient amount of intertumoural stroma in biopsies. Nonetheless, interobserver variability proved to be good to excellent. High stromal TILs (TILstr) and intratumoural TILs (TILtum) were both correlated to favourable overall survival and multivariate analysis showed TILstr to be the sole independent prognostic factor in OPSCC. The IBWG-proposed TIL quantification method is feasible and reproducible in OPSCC and provides valuable prognostic information regarding clinicopathological characteristics and overall survival. The use of this standardised methodology may facilitate implementation of TILs scoring as a prognostic biomarker in OPSCC.

Immuno-Oncological Biomarkers for Squamous Cell Cancer of the Head and Neck: Current State of the Art and Future Perspectives.

The era of immune checkpoint inhibitors has altered the therapeutic landscape in squamous cell cancer of the head and neck (SCCHN). Our knowledge about the tumor microenvironment has fueled the research in SCCHN, leading to several well-known and less-known prognostic and predictive biomarkers. The clinical staging, p16/HPV status, and PD-L1 expression are currently the main tools for assessing the patients' diagnosis and prognosis. However, several novel biomarkers have been thoroughly investigated, some reaching actual significant clinical contributions. The untangling of the immune infiltrate with the subtyping of tissue-associated tumor infiltrating lymphocytes, tumor-associated macrophages, and circulating blood-based biomarkers are an interesting avenue to be further explored and prospectively assessed. Although PD-L1 expression remains the most important response predictor for immune checkpoint inhibitors, several flaws impede proper assessment such as technical issues, different scoring protocol, and intra-, inter-, and temporal heterogeneity. In addition, the construction of an immune-related gene panel has been proposed as a prognostic and predictive stratification but lacks consensus. Recently, the role of microbioma have also been explored regarding its systemic and antitumor immunity. This review gives a comprehensive overview of the aforementioned topics in SCCHN. To this end, the integration of these clinically advantageous biomarkers via construction of an immunogram or nomogram could be an invaluable tool for SCCHN in future prospects.

Managing viral hepatitis in cancer patients under immune checkpoint inhibitors: should we take the risk?

More patients with chronic hepatitis B and C infection are being exposed to immune checkpoint inhibitors (ICIs), but the safety and efficacy of ICIs in patients with chronic viral hepatitis are still poorly described. To explore this interaction, we identified eight studies of cancer patients with viral hepatitis treated with one or more ICIs, formally assessed tumor responses and safety by grading liver dysfunction. ICIs appear to be relatively safe in HBV/HCV-infected patients, and hepatitis related to viral reactivation is rare. In some patients, viral load regressed during ICI treatment, so immune checkpoints may play a role in viral clearance. HBV/HCV do not appear to be a contraindication to ICIs, although careful clinical and biochemical follow-up is recommended and, whenever necessary, antiviral therapy commenced.