CD8 infiltration is associated with disease control and tobacco exposure in intermediate-risk oropharyngeal cancer.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
14 01 2020
14 01 2020
Historique:
received:
25
07
2019
accepted:
20
12
2019
entrez:
16
1
2020
pubmed:
16
1
2020
medline:
11
11
2020
Statut:
epublish
Résumé
Oropharyngeal squamous cell carcinoma (OPSCC) incidence is increasing at a nearly epidemic rate, largely driven by the human papillomavirus (HPV). Despite the generally favorable clinical outcomes of patients with HPV driven (HPV+) OPSCC, a significant subset of HPV tumors associated with tobacco exposure have diminished treatment response and worse survival. The tumor immune microenvironment (TIME) has been shown to be a critical driver of treatment response and oncologic outcomes in OPSCC generally and HPV+ OPSCC more specifically. However, the impact of tobacco exposure on the TIME in OPSCC patients remains unclear. We analyzed the relationship between TIME, tobacco exposure and clinical outcomes in OPSCC patients (n = 143) with extensive tobacco exposure (median pack-years = 40). P16 overexpression, a surrogate marker of HPV association, was a strong predictor of relapse-free (RFS) and overall survival (OS) (p < 0.001, p < 0.001 respectively) regardless of tobacco exposure and associated strongly with differential infiltration of the tumor by both CD3 and CD8 lymphocytes measured via immunohistochemistry (p < 001, p < 0.001 respectively). CD3 and CD8 infiltration was a strong predictor of RFS and OS and associated strongly with disease stage (AJCC 8
Identifiants
pubmed: 31937831
doi: 10.1038/s41598-019-57111-5
pii: 10.1038/s41598-019-57111-5
pmc: PMC6959290
doi:
Substances chimiques
CD8 Antigens
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
243Subventions
Organisme : NCI NIH HHS
ID : T32 CA174647
Pays : United States
Organisme : NIDCR NIH HHS
ID : U01 DE028233
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA097007
Pays : United States
Organisme : NIDCR NIH HHS
ID : R01 DE025248
Pays : United States
Organisme : NIDCR NIH HHS
ID : R56 DE025248
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA214825
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016672
Pays : United States
Organisme : NIBIB NIH HHS
ID : R25 EB025787
Pays : United States
Références
Ang, K. K. et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med 363, 24–35, https://doi.org/10.1056/NEJMoa0912217 (2010).
doi: 10.1056/NEJMoa0912217
pubmed: 2943767
pmcid: 2943767
Dahlstrom, K. R. et al. An evolution in demographics, treatment, and outcomes of oropharyngeal cancer at a major cancer center: a staging system in need of repair. Cancer 119, 81–89, https://doi.org/10.1002/cncr.27727 (2013).
doi: 10.1002/cncr.27727
pubmed: 22736261
Gillison, M. L. et al. Distinct risk factor profiles for human papillomavirus type 16-positive and human papillomavirus type 16-negative head and neck cancers. J Natl Cancer Inst 100, 407–420, https://doi.org/10.1093/jnci/djn025 (2008).
doi: 10.1093/jnci/djn025
pubmed: 18334711
Gleber-Netto, F. O. et al. Variations in HPV function are associated with survival in squamous cell carcinoma. JCI Insight 4, https://doi.org/10.1172/jci.insight.124762 (2019).
Sandulache, V. C. et al. Oropharyngeal squamous cell carcinoma in the veteran population: Association with traditional carcinogen exposure and poor clinical outcomes. Head Neck 37, 1246–1253, https://doi.org/10.1002/hed.23740 (2015).
doi: 10.1002/hed.23740
pubmed: 24801106
pmcid: 4496314
Vawda, N., Banerjee, R. N. & Debenham, B. J. Impact of Smoking on Outcomes of HPV-related Oropharyngeal Cancer Treated with Primary Radiation or Surgery. Int J Radiat Oncol Biol Phys 103, 1125–1131, https://doi.org/10.1016/j.ijrobp.2018.11.046 (2019).
doi: 10.1016/j.ijrobp.2018.11.046
pubmed: 30513378
Jung, A. C. et al. CD8-alpha T-cell infiltration in human papillomavirus-related oropharyngeal carcinoma correlates with improved patient prognosis. Int J Cancer 132, E26–36, https://doi.org/10.1002/ijc.27776 (2013).
doi: 10.1002/ijc.27776
Oguejiofor, K. et al. Stromal infiltration of CD8 T cells is associated with improved clinical outcome in HPV-positive oropharyngeal squamous carcinoma. Br J Cancer 113, 886–893, https://doi.org/10.1038/bjc.2015.277 (2015).
doi: 10.1038/bjc.2015.277
pubmed: 26313665
pmcid: 4578081
Koneva, L. A. et al. HPV Integration in HNSCC Correlates with Survival Outcomes, Immune Response Signatures, and Candidate Drivers. Mol Cancer Res 16, 90–102, https://doi.org/10.1158/1541-7786.MCR-17-0153 (2018).
doi: 10.1158/1541-7786.MCR-17-0153
pubmed: 28928286
De Meulenaere, A. et al. Tumor PD-L1 status and CD8(+) tumor-infiltrating T cells: markers of improved prognosis in oropharyngeal cancer. Oncotarget 8, 80443–80452, https://doi.org/10.18632/oncotarget.19045 (2017).
doi: 10.18632/oncotarget.19045
pubmed: 29113315
pmcid: 5655210
Fakhry, C. et al. Validation of NRG oncology/RTOG-0129 risk groups for HPV-positive and HPV-negative oropharyngeal squamous cell cancer: Implications for risk-based therapeutic intensity trials. Cancer 125, 2027–2038, https://doi.org/10.1002/cncr.32025 (2019).
doi: 10.1002/cncr.32025
pubmed: 30913305
Sandulache, V. C. et al. Innovations in risk-stratification and treatment of Veterans with oropharynx cancer; roadmap of the 2019 Field Based Meeting. Oral Oncol, 104440, https://doi.org/10.1016/j.oraloncology.2019.104440 (2019).
Desrichard, A. et al. Tobacco Smoking-Associated Alterations in the Immune Microenvironment of Squamous Cell Carcinomas. J Natl Cancer Inst 110, 1386–1392, https://doi.org/10.1093/jnci/djy060 (2018).
doi: 10.1093/jnci/djy060
pubmed: 29659925
pmcid: 6292793
Fakhry, C. et al. Human papillomavirus and overall survival after progression of oropharyngeal squamous cell carcinoma. J Clin Oncol 32, 3365–3373, https://doi.org/10.1200/JCO.2014.55.1937 (2014).
doi: 10.1200/JCO.2014.55.1937
pubmed: 24958820
pmcid: 4195851
Gillison, M. L. et al. Tobacco smoking and increased risk of death and progression for patients with p16-positive and p16-negative oropharyngeal cancer. J Clin Oncol 30, 2102–2111, https://doi.org/10.1200/JCO.2011.38.4099 (2012).
doi: 10.1200/JCO.2011.38.4099
pubmed: 22565003
pmcid: 3397696
Gupta, S. M. & Mania-Pramanik, J. Molecular mechanisms in progression of HPV-associated cervical carcinogenesis. J Biomed Sci 26, 28, https://doi.org/10.1186/s12929-019-0520-2 (2019).
doi: 10.1186/s12929-019-0520-2
pubmed: 31014351
pmcid: 6477741
Dogan, S. et al. Identification of prognostic molecular biomarkers in 157 HPV-positive and HPV-negative squamous cell carcinomas of the oropharynx. Int J Cancer 145, 3152–3162, https://doi.org/10.1002/ijc.32412 (2019).
doi: 10.1002/ijc.32412
pubmed: 31093971
Shiels, M. S. et al. Cigarette smoking and variations in systemic immune and inflammation markers. J Natl Cancer Inst 106, https://doi.org/10.1093/jnci/dju294 (2014).
Bauer, M. et al. Tobacco smoking differently influences cell types of the innate and adaptive immune system-indications from CpG site methylation. Clin Epigenetics 7, 83, https://doi.org/10.1186/s13148-016-0249-7 (2015).
doi: 10.1186/s13148-016-0249-7
pubmed: 27493699
Applebaum, K. M. et al. Smoking modifies the relationship between XRCC1 haplotypes and HPV16-negative head and neck squamous cell carcinoma. Int J Cancer 124, 2690–2696, https://doi.org/10.1002/ijc.24256 (2009).
doi: 10.1002/ijc.24256
pubmed: 19230024
pmcid: 2746567
Bauer, M. et al. A varying T cell subtype explains apparent tobacco smoking induced single CpG hypomethylation in whole blood. Clin Epigenetics 7, 81, https://doi.org/10.1186/s13148-015-0113-1 (2015).
doi: 10.1186/s13148-015-0113-1
pubmed: 26246861
pmcid: 4526203
Lee, J., Taneja, V. & Vassallo, R. Cigarette smoking and inflammation: cellular and molecular mechanisms. J Dent Res 91, 142–149, https://doi.org/10.1177/0022034511421200 (2012).
doi: 10.1177/0022034511421200
pubmed: 21876032
pmcid: 3261116
Su, D. et al. Distinct Epigenetic Effects of Tobacco Smoking in Whole Blood and among Leukocyte Subtypes. PLoS One 11, e0166486, https://doi.org/10.1371/journal.pone.0166486 (2016).
doi: 10.1371/journal.pone.0166486
pubmed: 27935972
pmcid: 5147832
Lydiatt, W. M. et al. Head and Neck cancers-major changes in the American Joint Committee on cancer eighth edition cancer staging manual. CA Cancer J Clin 67, 122–137, https://doi.org/10.3322/caac.21389 (2017).
doi: 10.3322/caac.21389
pubmed: 28128848
Lai, S. et al. Prognostic Significance of p16 Cellular Localization in Oropharyngeal Squamous Cell Carcinoma. Ann Clin Lab Sci 46, 132–139 (2016).
pubmed: 27098618
Hoffman, H. T. et al. Laryngeal cancer in the United States: changes in demographics, patterns of care, and survival. Laryngoscope 116, 1–13, https://doi.org/10.1097/01.mlg.0000236095.97947.26 (2006).
doi: 10.1097/01.mlg.0000236095.97947.26
pubmed: 16946667
Sandulache, V. C. et al. High-Risk TP53 Mutations Are Associated with Extranodal Extension in Oral Cavity Squamous Cell Carcinoma. Clin Cancer Res 24, 1727–1733, https://doi.org/10.1158/1078-0432.CCR-17-0721 (2018).
doi: 10.1158/1078-0432.CCR-17-0721
pubmed: 29330202
pmcid: 5884733
Gillison, M. L. et al. Radiotherapy plus cetuximab or cisplatin in human papillomavirus-positive oropharyngeal cancer (NRG Oncology RTOG 1016): a randomised, multicentre, non-inferiority trial. Lancet 393, 40–50, https://doi.org/10.1016/S0140-6736(18)32779-X (2019).
doi: 10.1016/S0140-6736(18)32779-X
pubmed: 30449625
Mehanna, H. et al. Radiotherapy plus cisplatin or cetuximab in low-risk human papillomavirus-positive oropharyngeal cancer (De-ESCALaTE HPV): an open-label randomised controlled phase 3 trial. Lancet 393, 51–60, https://doi.org/10.1016/S0140-6736(18)32752-1 (2019).
doi: 10.1016/S0140-6736(18)32752-1
pubmed: 30449623
pmcid: 6319250
Sandulache, V. C., Wilde, D. C., Sturgis, E. M., Chiao, E. & Sikora, A. G. A hidden epidemic of “intermediate risk” oropharynx cancer. Laryngoscope Investig Otolaryngol early view (2019).
Pignon, J. P., le Maitre, A., Maillard, E., Bourhis, J. & Group, M.-N. C. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): an update on 93 randomised trials and 17,346 patients. Radiother Oncol 92, 4–14, https://doi.org/10.1016/j.radonc.2009.04.014 (2009).
doi: 10.1016/j.radonc.2009.04.014
pubmed: 19446902
Blanchard, P. et al. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): a comprehensive analysis by tumour site. Radiother Oncol 100, 33–40, https://doi.org/10.1016/j.radonc.2011.05.036 (2011).
doi: 10.1016/j.radonc.2011.05.036
pubmed: 21684027
Park, J. et al. Positivity Rates in Oropharyngeal and Nonoropharyngeal Head and Neck Cancer in the VA. Fed Pract 35, S44–S47 (2018).
pubmed: 30766403
pmcid: 6248148
Feinstein, A. J., Shay, S. G., Chang, E., Lewis, M. S. & Wang, M. B. Treatment outcomes in veterans with HPV-positive head and neck cancer. Am J Otolaryngol 38, 188–192, https://doi.org/10.1016/j.amjoto.2017.01.005 (2017).
doi: 10.1016/j.amjoto.2017.01.005
pubmed: 28342482
Zevallos, J. P. et al. Impact of race on oropharyngeal squamous cell carcinoma presentation and outcomes among veterans. Head Neck 38, 44–50, https://doi.org/10.1002/hed.23836 (2016).
doi: 10.1002/hed.23836
pubmed: 24992520
Ferris, R. L. et al. Nivolumab vs investigator’s choice in recurrent or metastatic squamous cell carcinoma of the head and neck: 2-year long-term survival update of CheckMate 141 with analyses by tumor PD-L1 expression. Oral Oncol 81, 45–51, https://doi.org/10.1016/j.oraloncology.2018.04.008 (2018).
doi: 10.1016/j.oraloncology.2018.04.008
pubmed: 29884413
pmcid: 6563923
Ferris, R. & Gillison, M. L. Nivolumab for Squamous-Cell Cancer of Head and Neck. N Engl J Med 376, 596, https://doi.org/10.1056/NEJMc1615565 (2017).
doi: 10.1056/NEJMc1615565
pubmed: 28177863
Ferris, R. L. et al. Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck. N Engl J Med 375, 1856–1867, https://doi.org/10.1056/NEJMoa1602252 (2016).
doi: 10.1056/NEJMoa1602252
pubmed: 27718784
pmcid: 5564292
Ferris, R. L. et al. Nivolumab in Patients with Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck: Efficacy and Safety in CheckMate 141 by Prior Cetuximab Use. Clin Cancer Res 25, 5221–5230, https://doi.org/10.1158/1078-0432.CCR-18-3944 (2019).
doi: 10.1158/1078-0432.CCR-18-3944
pubmed: 31239321
Gillison, M. L. et al. CheckMate 141: 1-Year Update and Subgroup Analysis of Nivolumab as First-Line Therapy in Patients with Recurrent/Metastatic Head and Neck Cancer. Oncologist 23, 1079–1082, https://doi.org/10.1634/theoncologist.2017-0674 (2018).
doi: 10.1634/theoncologist.2017-0674
pubmed: 29866947
pmcid: 6221824
Burtness, B. et al. Protocol-specified final analysis of the phase 3 KEYNOTE-048 trial of pembrolizumab (pembro) as first-line therapy for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). J Clin Oncol 37, 6000 (2019).
doi: 10.1200/JCO.2019.37.15_suppl.6000
Staaf, J. et al. Relation between smoking history and gene expression profiles in lung adenocarcinomas. BMC Med Genomics 5, 22, https://doi.org/10.1186/1755-8794-5-22 (2012).
doi: 10.1186/1755-8794-5-22
pubmed: 22676229
pmcid: 3447685
Foy, J. P. et al. The immune microenvironment of HPV-negative oral squamous cell carcinoma from never-smokers and never-drinkers patients suggests higher clinical benefit of IDO1 and PD1/PD-L1 blockade. Ann Oncol 28, 1934–1941, https://doi.org/10.1093/annonc/mdx210 (2017).
doi: 10.1093/annonc/mdx210
pubmed: 28460011