Background: Accurate prognostic stratification of human papillomavirus-associated oropharyngeal cancers (HPVþOPSCC) is required to identify patients potentially suitable for treatment deintensification. We evaluated the prognostic significance of CD103, a surface marker associated with tissue-resident memory T cells (T RM s), in two independent cohorts of patients with HPVþOPSCC.Patients and methods: The abundance and distribution of CD103 þ immune cells were quantified using immunohistochemistry in a cohort of 189 HPVþOPSCC patients treated with curative intent and correlated with outcome. Findings were then validated in an independent cohort comprising 177 HPVþOPSCCs using univariable and multivariable analysis. Intratumoral CD103 þ immune cells were characterized by multispectral fluorescence immunohistochemistry and gene expression analysis.Results: High intratumoral abundance of CD103 þ immune cells using a 30% cut-off was found in 19.8% of tumors in the training cohort of HPVþOPSCC patients and associated with excellent prognosis for overall survival (OS) with adjusted hazard ratio (HR) of 0.13 [95% confidence interval (CI) 0.02-0.94, P ¼ 0.004]. In the independent cohort of HPVþOPSCCs, 20.4% had high intratumoral CD103 þ abundance and an adjusted HR for OS of 0.16 (95% CI 0.02-1.22, P ¼ 0.02). Five year OS of patients with high intratumoral CD103 was 100% across both cohorts. The C-statistic for the multivariate prognostic model with stage and age was significantly improved in both cohorts with the addition of intratumoral CD103 þ cell abundance. On the basis of spatial location, co-expression of CD8 and CD69, and gene expression profiles, intratumoral CD103 þ cells were consistent with T RM s.
Conclusion:Quantification of intratumoral CD103 þ immune cell abundance provides prognostic information beyond that provided by clinical parameters such as TNM-staging, identifying a population of low risk HPVþOPSCC patients who are good candidates for trials of deintensification strategies.
A man in his 20s presents to the emergency department after a water skiing accident and was diagnosed with a grade 3 left renal laceration. He subsequently required cystoscopic insertion of a ureteric stent after failing a trial of conservative management. Over the next 9 months, he re-presented to the hospital twice with increasing flank pain and fevers. Subsequent imaging demonstrated interval progression of the retroperitoneal haematoma with a suspicious calcified lower pole lesion which was biopsied subsequently and revealed malignant tissue. External compression of the kidney by this large haematoma was also thought to be contributing to a state of Page kidney. The patient underwent definitive management with an open left-sided radical nephrectomy which confirmed type 2 papillary renal cell carcinoma. The patient is now normotensive and back to his baseline function. He will undergo surveillance CT imaging and be referred to familial genetic services.
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