HLA Class I Loss and Resistance to Immunotherapy in Pulmonary Metastasis of Hypopharyngeal Cancer

Although immune checkpoint inhibitors (ICIs) can be remarkably effective in the treatment of unresectable recurrent or metastatic carcinoma of the head and neck, even in cases of a marked response, some lesions may remain partially refractory or new lesions may emerge. However, why ICIs sometimes produce such a patchy pattern of therapeutic effects remains unclear.

A 62-year-old patient with advanced hypopharyngeal squamous cell carcinoma who developed pulmonary metastasis after surgery followed by postoperative chemoradiotherapy presented to our department. After initiating ICI therapy, the patient initially achieved complete remission; however, a new pulmonary lesion subsequently appeared and was surgically removed. The patient has since remained in durable remission with continued long-term ICI therapy. Immunohistochemical analysis comparing the new pulmonary lesion with the original hypopharyngeal tumor revealed that cancer cells in the primary lesion were positive for HLA class I and b2-microglobulin, whereas staining for these antigens was negative in cancer cells of the recurrent pulmonary lesion. Cancer cells in the primary lesion exhibited ectopic expression of HLA class II, but no expression was detected in cancer cells of recurrent lesions.

In the pulmonary lesion that did not respond to ICIs, a loss of HLA class I and b2-microglobulin expression was observed. These findings suggest that the reduced antigen-presenting capacity of cancer cells may contribute to immune escape.