Tingyu Liu1, Max Greenberg2, Carissa Wentland3, Brandon Sepe2, Sarah Bowe4, Gillian Diercks4, Tiffany Huynh5, Mari Mino-Kenudson5, Richard Schlegel6, David Kodack1, Cyril Benes2, Jeffrey Engelman1, Christopher Hartnick7. 1. Novartis Institutes for Biomedical Research, 250 Massachusetts Ave, Cambridge, MA 02139, United States. 2. Massachusetts General Hospital Cancer Center, 55 Fruit St, Boston, MA 02114, United States. 3. Department of Otolaryngology Head and Neck Surgery, University Hospital Cleveland Medical Center, 11100 Euclid Ave, Cleveland, OH 44106, United States. 4. Pediatric Otolaryngology Service, Massachusetts Eye and Ear Infirmary, 243 Charles St, Boston, MA 02114, United States. 5. Department of Pathology, Massachusetts General Hospital, 55 Fruit St, Boston, MA 02114, United States. 6. Department of Pathology, Georgetown University Medical School, 3800 Reservoir Rd NW, Washington, DC 20007, United States. 7. Pediatric Otolaryngology Service, Massachusetts Eye and Ear Infirmary, 243 Charles St, Boston, MA 02114, United States. Electronic address: christopher_hartnick@meei.harvard.edu.
Abstract
INTRODUCTION: Tumor immunotherapy have broadened therapeutic options for tumor treatment. The role of immune function in juvenile recurrent respiratory papillomatosis (JRRP) has not been investigated. Applying immunoblockade inhibitors as a novel disease treatment is unclear. Our study, for the first time, evaluates immune infiltration and immuno-suppressive molecule expression in JRRP. Our study provides insights in possibly treating this disease with tumor immunotherapies. We aimed to determine expression of programmed death-ligand 1 (PD-L1), a cancer escape protein, and presence of CD8+ T cell infiltration in tumor microenvironment. MATERIAL AND METHODS: Seven patients with JRRP (mean age: 7.43; age range 3-17) in this study routinely have their tumors surgical debulked at Massachusetts Eye and Ear Infirmary. Following surgery, samples were de-identified and sent to pathology where they were stained and analyzed. RESULTS: Six out of seven patients expressed PD-L1 on tumor cells to various extents. Three patients showed concurrent PD-L1 expression on tumor cells and abundant CD8+ tumor infiltrating lymphocytes as well as PD-L1+ stromal lymphocytes, while PD-L1 expression on tumor cells were not associated with CD8+ tumor infiltrating T cells nor PD-L1+ stromal lymphocytes in the other three patients. HPV 6/11 and p16 was detected in all the patients. There appeared to be no correlation between either PD-L1 expression and CD8+ infiltration and clinical severity as measured by both the number of surgeries per year or Derkay score. CONCLUSIONS: Despite a small cohort, the expression of p16 and HPV 6/11 in all of the patients confirms the tissues were HPV tumor cells. PD-L1 expression was detected in the vast majority of tumor samples, while inflammatory cell compartments showed a higher degree of variation. Expression of PD-L1 on tumor cells but not inflammatory cells raises the possibility of a tumor cell intrinsic manner of PD-L1 expression. In contrast, a group of patients showed PD-L1 positivity in both tumor and inflammatory cells along with abundant CD8+ tumor infiltrating lymphocytes, suggesting adoptive immune resistance in these tumors and potential benefits from tumor immunotherapy.
INTRODUCTION:Tumor immunotherapy have broadened therapeutic options for tumor treatment. The role of immune function in juvenile recurrent respiratory papillomatosis (JRRP) has not been investigated. Applying immunoblockade inhibitors as a novel disease treatment is unclear. Our study, for the first time, evaluates immune infiltration and immuno-suppressive molecule expression in JRRP. Our study provides insights in possibly treating this disease with tumor immunotherapies. We aimed to determine expression of programmed death-ligand 1 (PD-L1), a cancer escape protein, and presence of CD8+ T cell infiltration in tumor microenvironment. MATERIAL AND METHODS: Seven patients with JRRP (mean age: 7.43; age range 3-17) in this study routinely have their tumors surgical debulked at Massachusetts Eye and Ear Infirmary. Following surgery, samples were de-identified and sent to pathology where they were stained and analyzed. RESULTS: Six out of seven patients expressed PD-L1 on tumor cells to various extents. Three patients showed concurrent PD-L1 expression on tumor cells and abundant CD8+ tumor infiltrating lymphocytes as well as PD-L1+ stromal lymphocytes, while PD-L1 expression on tumor cells were not associated with CD8+ tumor infiltrating T cells nor PD-L1+ stromal lymphocytes in the other three patients. HPV 6/11 and p16 was detected in all the patients. There appeared to be no correlation between either PD-L1 expression and CD8+ infiltration and clinical severity as measured by both the number of surgeries per year or Derkay score. CONCLUSIONS: Despite a small cohort, the expression of p16 and HPV 6/11 in all of the patients confirms the tissues were HPV tumor cells. PD-L1 expression was detected in the vast majority of tumor samples, while inflammatory cell compartments showed a higher degree of variation. Expression of PD-L1 on tumor cells but not inflammatory cells raises the possibility of a tumor cell intrinsic manner of PD-L1 expression. In contrast, a group of patients showed PD-L1 positivity in both tumor and inflammatory cells along with abundant CD8+ tumor infiltrating lymphocytes, suggesting adoptive immune resistance in these tumors and potential benefits from tumor immunotherapy.
Authors: Ben C Creelan; M Usman Ahmad; Frank J Kaszuba; Farah K Khalil; Allison W Welsh; Metin Ozdemirli; Nazaneen N Grant; Deepa S Subramaniam Journal: Oncologist Date: 2019-03-06
Authors: Carol C Cheung; Penny Barnes; Gilbert Bigras; Scott Boerner; Jagdish Butany; Fiorella Calabrese; Christian Couture; Jean Deschenes; Hala El-Zimaity; Gabor Fischer; Pierre O Fiset; John Garratt; Laurette Geldenhuys; C Blake Gilks; Marius Ilie; Diana Ionescu; Hyun J Lim; Lisa Manning; Adnan Mansoor; Robert Riddell; Catherine Ross; Sinchita Roy-Chowdhuri; Alan Spatz; Paul E Swanson; Victor A Tron; Ming-Sound Tsao; Hangjun Wang; Zhaolin Xu; Emina E Torlakovic Journal: Appl Immunohistochem Mol Morphol Date: 2019 Nov/Dec