Current events in immunotherapy for upper aerodigestive tract cancer

Head and neck (HN) carcinomas (mostly represented by squamous cell carcinomas [SCC]) still have a poor prognosis, which could be dramatically improved with immunotherapy. Tumor's microenvironment changes, caused by many endogenous or exogenous events, can correlate with prognosis and therapeutic response. Here, we review recent data regarding HNSCC, nasopharyngeal carcinomas (NPC) and salivary gland malignant tumors, all three being potential target of immunotherapies. About half of HNSCC exhibit PD-L1 expression, this expression being upregulated in HPV-positive tumors. In recent clinical trials, a better therapeutic response to anti-PD-1 has been obtained in patients with higher PD-L1 expression. Food and Drug Administration (FDA) approved the use of these therapeutics without the screening of patients regarding PD-L1 status. Activation status, density and localisation of TIL as well as PD-L2, γ-interferon, inflammatory cytokines, epithelial-mesenchymal transition phenotype and mutational burden may all be potential therapeutic response markers. In Epstein-Barr Virus (EBV)-induced nasopharyngeal non-keratinizing cancer, PD-L1 is over-expressed compared to EBV negative-tumors. A 22 % response rate has been observed under anti-PD-1 treatment, among PD-L1-positive HNSCC patients. There is little data regarding microenvironment of salivary gland cancer. PD-L1 shows great heterogeneity in localisation, when expressed. A 11 % response rate has been obtained under anti-PD-1 treatment among PD-L1-positive NPC patients. A better understanding of immune checkpoint regulation processes needs to be achieved to allow patients with HN carcinomas to benefit from these promising immunotherapies.