Top

Published in:

01-02-2019 | Original Article

Analysis of tumor-infiltrating CD103 resident memory T-cell content in recurrent laryngeal squamous cell carcinoma

Authors: Jacqueline E. Mann, Joshua D. Smith, Andrew C. Birkeland, Emily Bellile, Paul Swiecicki, Michelle Mierzwa, Steven B. Chinn, Andrew G. Shuman, Kelly M. Malloy, Keith A. Casper, Scott A. McLean, Jeffery S. Moyer, Gregory T. Wolf, Carol R. Bradford, Mark E. Prince, Thomas E. Carey, Jonathan B. McHugh, Matthew E. Spector, J. Chad Brenner

Published in: Cancer Immunology, Immunotherapy | Issue 2/2019

Abstract

Background

Recurrent laryngeal squamous cell carcinomas (LSCCs) are associated with poor outcomes, without reliable biomarkers to identify patients who may benefit from adjuvant therapies. Given the emergence of tumor-infiltrating lymphocytes (TIL) as a biomarker in head and neck squamous cell carcinoma, we generated predictive models to understand the utility of CD4⁺, CD8⁺ and/or CD103⁺ TIL status in patients with advanced LSCC.

Methods

Tissue microarrays were constructed from salvage laryngectomy specimens of 183 patients with recurrent/persistent LSCC and independently stained for CD4⁺, CD8⁺, and CD103⁺ TIL content. Cox proportional hazards regression analysis was employed to assess combinations of CD4⁺, CD8⁺, and CD103⁺ TIL levels for prediction of overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) in patients with recurrent/persistent LSCC.

Results

High tumor CD103⁺ TIL content was associated with significantly improved OS, DSS, and DFS and was a stronger predictor of survival in recurrent/persistent LSCC than either high CD8⁺ or CD4⁺ TIL content. On multivariate analysis, an “immune-rich” phenotype, in which tumors were enriched for both CD103⁺ and CD4⁺ TILs, conferred a survival benefit (OS hazard ratio: 0.28, p = 0.0014; DSS hazard ratio: 0.09, p = 0.0015; DFS hazard ratio: 0.18, p = 0.0018) in recurrent/persistent LSCC.

Conclusions

An immune profile driven by CD103⁺ TIL content, alone and in combination with CD4⁺ TIL content, is a prognostic biomarker of survival in patients with recurrent/persistent LSCC. Predictive models described herein may thus prove valuable in prognostic stratification and lead to personalized treatment paradigms for this patient population.

Available only for authorised users

Forastiere AA, Zhang Q, Weber RS, Maor MH, Goepfert H, Pajak TF et al (2013) Long-term results of RTOG 91–11: a comparison of three nonsurgical treatment strategies to preserve the larynx in patients with locally advanced larynx cancer. J Clin Oncol 31:845–852CrossRefPubMed

Forastiere AA, Weber RS, Trotti A (2015) Organ preservation for advanced larynx cancer: issues and outcomes. J Clin Oncol 33:3262–3268CrossRefPubMedPubMedCentral

Wolf GT, Fisher SG, Hong WK, Hillman R, Spaulding M, Laramore GE et al (1991) Induction chemotherapy plus radiation compared with surgery plus radiation in patients with advanced laryngeal cancer. N Engl J Med 324:1685–1690CrossRefPubMed

van der Putten L, de Bree R, Kuik DJ, Rietveld DH, Buter J, Eerenstein SE et al (2011) Salvage laryngectomy: oncological and functional outcome. Oral Oncol 47:296–301CrossRefPubMed

Birkeland AC, Beesley L, Bellile E, Rosko AJ, Hoesli R, Chinn SB et al (2017) Predictors of survival after total laryngectomy for recurrent/persistent laryngeal squamous cell carcinoma. Head Neck 39:2512–2518CrossRefPubMedPubMedCentral

Morris LG, Chandramohan R, West L, Zehir A, Chakravarty D, Pfister DG et al (2017) The molecular landscape of recurrent and metastatic head and neck cancers: insights from a precision oncology sequencing platform. JAMA Oncol 3:244–255CrossRefPubMedPubMedCentral

Mann JE, Hoesli R, Michmerhuizen NL, Devenport SN, Ludwig M, Vandenberg TR et al (2017) Surveilling the potential for precision medicine-driven PD-1/PD-L1-targeted therapy in HNSCC. J Cancer 8:332–344CrossRefPubMedPubMedCentral

Lei Y, Xie Y, Tan YS, Prince ME, Moyer JS, Nor J et al (2016) Telltale tumor infiltrating lymphocytes (TIL) in oral, head & neck cancer. Oral Oncol 61:159–165CrossRefPubMedPubMedCentral

Hoesli R, Birkeland AC, Rosko AJ, Issa M, Chow KL, Michmerhuizen NL et al (2018) Proportion of CD4 and CD8 tumor infiltrating lymphocytes predicts survival in persistent/recurrent laryngeal squamous cell carcinoma. Oral Oncol 77:83–89CrossRefPubMed

10.

Wolf GT, Hudson JL, Peterson KA, Miller HL, McClatchey KN (1986) Lymphocyte subpopulations infiltrating squamous carcinomas of the head and neck: correlations with extent of tumor and prognosis. Otolaryngol Head Neck Surg 95:142–152CrossRefPubMed

11.

Wansom D, Light E, Thomas D, Worden F, Prince M, Urba S et al (2012) Infiltrating lymphocytes and human papillomavirus-16 associated oropharynx cancer. Laryngoscope 122:121–127CrossRefPubMedPubMedCentral

12.

Wolf GT, Chepeha DB, Bellile E, Nguyen A, Thomas D, McHugh J, The University of Michigan Head and Neck SPORE Program (2015) Tumor infiltrating lymphocytes (TIL) and prognosis in oral cavity squamous carcinoma: a preliminary study. Oral Oncol 51:90–95CrossRefPubMed

13.

Nguyen N, Bellile E, Thomas D, McHugh J, Rozek L, Virani S et al (2016) Tumor infiltrating lymphocytes and survival in patients with head and neck squamous cell carcinoma. Head Neck 38:1074–1084CrossRefPubMedPubMedCentral

14.

Anz D, Mueller W, Golic M, Kunz WG, Rapp M, Koelzer VH et al (2011) CD103 is a hallmark of tumor-infiltrating regulatory T cells. Int J Cancer 129:2417–2426CrossRefPubMed

15.

Ganesan A, Clarke J, Wood O, Garrido-Martin EM, Chee SJ, Mellows T et al (2017) Tissue-resident memory features are linked to the magnitude of cytotoxic T cell responses in human lung cancer. Nature Immunol 18:940–950CrossRef

16.

Webb JR, Milne K, Watson P, deLeeuw RJ, Nelson BH (2014) Tumor-infiltrating lymphocytes expressing the tissue resident memory marker CD103 are associated with increased survival in high-grade serous ovarian cancer. Clin Cancer Res 20:434–444CrossRefPubMed

17.

Webb JR, Milne K, Nelson BH (2015) PD-1 and CD103 are widely coexpressed on prognostically favorable intraepithelial CD8 T cells in human ovarian cancer. Cancer Immunol Res 3:926–935CrossRefPubMed

18.

American Joint Committee on Cancer (2010) AJCC Cancer Staging Manual. 7th. Springer Press, ChicagoCrossRef

19.

Keck MK, Zuo Z, Khattri A, Stricker TP, Brown CD, Imanguli M et al (2015) Integrative analysis of head and neck cancer identifies two biologically distinct HPV and three non-HPV subtypes. Clin Cancer Res 21:870–881CrossRefPubMed

20.

Mandrekar JN, Mandrekar SJ, Cha SS (2003) Cutpoint determination methods in survival analysis using SAS. In: Proceedings of the 28th SAS users group international conference (SUGI) 261-28

21.

Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pages C et al (2006) Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science 313:1960–1964CrossRefPubMed

22.

Brambilla E, Le Teuff G, Marguet S, Lantuejoul S, Dunant A et al (2016) Prognostic effect of tumor lymphocytic infiltration in resectable non-small-cell lung cancer. J Clin Oncol 34:1123–1130CrossRef

23.

Jiang D, Liu Y, Wang H, Wang H, Song Q, Sujie A et al (2017) Tumour infiltrating lymphocytes correlate with improved survival in patients with esophageal squamous cell carcinoma. Sci Rep 7:44823CrossRefPubMedPubMedCentral

24.

Chen X, Gao L, Sturgis EM, Liang Z, Zhu Y, Xia X et al (2017) HPV16 DNA and integration in normal and malignant epithelium: implications for the etiology of laryngeal squamous cell carcinoma. Ann Oncol 28:1105–1110CrossRefPubMedPubMedCentral

25.

Zhang Y, Koneva LA, Virani S, Arthur AE, Virani A, Hall PB et al (2016) Subtypes of HPV-positive head and neck cancers are associated with HPV characteristics, copy number alterations, PIK3CA mutation, and pathway signatures. Clin Cancer Res 22:4735–4745CrossRefPubMedPubMedCentral

26.

Solomon B, Young RJ, Bressel M, Urban D, Hendry S, Thai A et al (2018) Prognostic significance of PD-L1⁺ and CD8⁺ immune cells in HPV⁺ oropharyngeal squamous cell carcinoma. Cancer Immunol Res 6:295–304CrossRefPubMed

27.

Mandal R, Senbabaoglu Y, Desrichard A, Havel JJ, Dalin MG, Riaz N et al (2016) The head and neck cancer immune landscape and its immunotherapeutic implications. JCI Insight 1:e89829CrossRefPubMedPubMedCentral

28.

Moskovitz J, Moy J, Ferris RL (2018) Immunotherapy for head and neck squamous cell carcinoma. Curr Oncol Rep 20:22CrossRefPubMedPubMedCentral

Title: Analysis of tumor-infiltrating CD103 resident memory T-cell content in recurrent laryngeal squamous cell carcinoma
Authors: Jacqueline E. Mann
Joshua D. Smith
Andrew C. Birkeland
Emily Bellile
Paul Swiecicki
Michelle Mierzwa
Steven B. Chinn
Andrew G. Shuman
Kelly M. Malloy
Keith A. Casper
Scott A. McLean
Jeffery S. Moyer
Gregory T. Wolf
Carol R. Bradford
Mark E. Prince
Thomas E. Carey
Jonathan B. McHugh
Matthew E. Spector
J. Chad Brenner
Publication date: 01-02-2019
Publisher: Springer Berlin Heidelberg
Published in: Cancer Immunology, Immunotherapy / Issue 2/2019
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-018-2256-3

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 2/2019

The nature of the human T cell response to the cancer antigen 5T4 is determined by the balance of regulatory and inflammatory T cells of the same antigen-specificity: implications for vaccine design

Inhibitory functions of PD-L1 and PD-L2 in the regulation of anti-tumor immunity in murine tumor microenvironment

Stromal interleukin-33 promotes regulatory T cell-mediated immunosuppression in head and neck squamous cell carcinoma and correlates with poor prognosis

Upregulation of tumor PD-L1 by neoadjuvant chemoradiotherapy (neoCRT) confers improved survival in patients with lymph node metastasis of locally advanced rectal cancers

Tumor-infiltrating immune cell subpopulations and programmed death ligand 1 (PD-L1) expression associated with clinicopathological and prognostic parameters in ependymoma

INT-HA induces M2-like macrophage differentiation of human monocytes via TLR4-miR-935 pathway

Keynote webinar | Spotlight on antibody–drug conjugates in cancer