Cutaneous squamous-cell carcinoma of the head-neck area refractory to chemo-radiotherapy: benefit from anti-PD-1 immunotherapy

Abstract

Objective: Radiotherapy provides excellent results in locally advanced cutaneous squamous-cell carcinoma of the head and neck area (cSCC-HN), with a 2-year local progression-free interval obtained for about 80% of patients. Overexpression of immune checkpoint co-inhibitory molecules, like PD-L1 (programmed death ligand 1), by cancer cells may define local immunosuppression, tumour escape from immune surveillance and reduced radiotherapy efficacy. Methods: A 65-year-old female, with a large exophytic cSCC-HN invading adjacent soft tissues, was treated with hypofractionated accelerated chemo-radiotherapy. The patient received four bi-weekly cycles of chemotherapy concurrently with eight fractions of 5.5 Gy (two fractions per week). Two months after the end of chemo-radiotherapy, the tumour was stable in dimensions, without any signs of symptomatic relief. The patient was, after that, treated with anti-PD-1 immunotherapy (nivolumab). The tumour gradually regressed, reaching partial response after four cycles and complete response after 16 cycles of nivolumab. No side-effects related to immunotherapy were recorded. The patient is alive and without evidence of disease 28 months after radiotherapy. Conclusions: Treatment of patients with chemo- and radio-resistant cSCC-HN with immunotherapy may optimize the efficacy of radiotherapy by stimulating immunological tumour rejection mechanisms. cSCC-HN patients who fail to respond to chemo-radiotherapy completely are expected to benefit the most from immunotherapy because of the radio-vaccination effect expected from the preceded radiotherapy.

Combining the past and present to advance immuno-radiotherapy of cancer

“…Abscopal responses were noted in 52% of patients. In addition, clinical experience suggests that immunotherapy after the failure of radiotherapy to control the local disease may lead to a complete response of the tumor [123]. This latter effect has been substantiated in the randomized PACIFIC study in patients with stage III non-smallcell lung cancer.…”

Feedback loop between hypoxia and energy metabolic reprogramming aggravates the radioresistance of cancer cells

“…PD-L1 upregulation prevents activation of T cells and NK cells [181]. Therefore, PD-L1-mediated immune escape is also an important cause of radioresistance [182][183][184]. Mechanisms underlying immunosuppression caused by radiation are summarized in Table 3.…”

“…[182] Cutaneous squamous-cell carcinoma of the head and neck area (cSCC-HN) [183] Prostate cancer [184] CircIGF2BP3 reduces PD-L1 ubiquitination Non-small cell lung cancer [185] DNA repair mitigates radiationinduced replication stress Breast cancer [186] Effect of regulation factor TGF-β, Functions of MIF, CCL2, CXCL5, CXCL8 and CXCL12 Rhabdomyosarcoma [187] STAT3 serine 727 phosphorylation Glioblastoma [188] CSC causes NK cells lose cytotoxicity Triple negative breast cancer [79] Upregulation of B7-H3 on circulating epithelial tumor cells (CETCs)…”

Expanding the role of combined immunochemotherapy and immunoradiotherapy in the management of head and neck cancer (Review)

“…Numerous antibodies have additionally been scrutinized in stage I/II preliminary studies for patients with HNSCC (160). Furthermore, laherparepvec, in combination with cisplatin and radiotherapy, showed an increase in survival rate (161,162). A phase II study on the combination of nivolumab with the synthetic long-peptide HPV-16 vaccine demonstrated promising outcomes, with a superior response compared with that of anti-PD-I treatment alone, thus supporting the need of further investigation on the use of combinatorial immunotherapy for higher clinical efficacy.…”