Interdigitating dendritic cell sarcoma of the supraglottic larynx

Background: Interdigitating dendritic cell sarcoma (IDCS) is an extremely rare neoplasm with sparse published literature, limited to case reports. This neoplasm arises from dendritic cells mainly within lymph nodes, however extranodal localization has been noted in the head and neck. Methods: Herein we present the first report of IDCS of the supraglottic larynx. A 35-year-old woman presented with odynophagia and dysphagia and was found to have an epiglottic primary lesion with bilateral regional lymphadenopathy. She was treated with transoral laser supraglottic laryngectomy, bilateral neck dissections, and postoperative radiation therapy. Results: Patient has no evidence of disease with 4 years of follow-up. Conclusion: Surgical resection with postoperative radiation therapy is a reasonable approach for management of loco-regionally advanced extranodal IDCS of the head and neck

Post-irradiation intratumoral heterogeneity modulates response to immune checkpoint inhibition therapy in a murine melanoma model

Purpose: The underlying mechanism for radiation as a potentiator of immune checkpoint inhibition (ICI) is unclear. We developed a novel murine model to investigate the effects of post-irradiation intratumoral heterogeneity (ITH) on response to ICI. Experimental design: Parental mouse melanoma B16F10 cells were irradiated in vitro (5Gy x 3 fractions), then an a priori determined number of resulting colonies were implanted in C57BL/6J immunocompetent mice creating syngeneic models of unirradiated (parental) and irradiated tumors with low (irradiated-L) and high (irradiated-H) ITH. Mice were treated with placebo, α-PD-L1, α-CTLA-4 or dual ICI. Murine tumors underwent whole exome sequencing (WES). Clinically correlated paired pre- and post-irradiation patient rectal adenocarcinoma samples underwent WES. Results: Irradiated-L tumors showed increased tumor mutational burden (TMB) and a sustained decrease in ITH. Irradiated-L tumors were predicted to express five neoantigens with high variant allele frequency/clonal distribution. Mice with irradiated-L and irradiated-H versus parental B16F10 tumors demonstrated longer overall survival with dual ICI. Only mice with irradiated-L tumors experienced an overall survival benefit with single agent ICI. Clinically correlated rectal adenocarcinoma samples showed similarly increased TMB and decreased ITH following irradiation. Conclusions: Post-irradiation ITH modulates ICI response in a murine melanoma model. Irradiation may offer a mechanism to widen the therapeutic window of ICI