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Lymphocytic Host Response to Oral Squamous Cell Carcinoma: An Adaptive T-Cell Response at the Tumor Interface

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Abstract

Lymphocytic host response (LHR) in the Risk Model is histologically quantified as the density of lymphocytes at the tumor interface (Brandwein-Gensler in Am J Surg Pathol, 34:676–688, 1; in, Am J Surg Pathol 29:167–178, 2). It is classified as strong, intermediate or weak, and is inversely associated with the risk of decreased time to disease progression. In this study, we test the hypothesis that strong LHR corresponds to a greater degree of adaptive cytotoxic T cell response as compared to moderate LHR. We studied resection specimens of primary oral squamous carcinoma classified as having either strong (n = 16), intermediate (n = 20) or weak (n = 4) LHR. CD20+, CD4+, & CD8+ cells were detected by immunohistochemistry and quantified at 40× with a grid; counting the 10 fields with the most lymphocytes at the tumor interface and within tumors. Mean counts/tumor were analyzed by the 2-sided T-test. Statistically significant differences were observed for interface CD8 cells with respect to strong versus moderate LHR, strong versus weak LHR, and moderate versus weak LHR, and tumor infiltrating CD8 cells with respect to strong versus weak LHR. Statistically significant differences were also observed for interface CD4 cells with respect to strong versus weak LHR, and moderate versus weak LHR. Statistically significant differences in interface B cell counts were seen with respect to strong versus weak LHR, and moderate versus weak LHR. Decreased CD8+ T cells were significantly associated with higher stage at presentation (P = 0.005); a direct, but nonsignificant correlation was seen between decreased CD8+ T cells and decreased survival time. Immune response at the tumor interface correlates with an adaptive T cell response; the degree of cytotoxic CD8+ cells infiltrate can distinguish between strong and intermediate LHR at the interface of oral carcinomas.

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References

  1. Brandwein-Gensler M, Smith RV, Wang B, Penner C, Theilken A, Broughel D, Schiff B, Owen RP, Smith J, Sarta C, Hebert T, Nason R, Ramer M, DeLacure M, Hirsch D, Myssiorek D, Heller K, Prystowsky M, Schlecht NF, Negassa A. Validation of the histologic risk model in a new cohort of patients with head and neck squamous cell carcinoma. Am J Surg Pathol. 2010;34:676–88.

    PubMed  Google Scholar 

  2. Brandwein-Gensler M, Teixeira MS, Lewis CM, Lee B, Rolnitzky L, Hille JJ, Genden E, Urken ML, Wang BY. Oral squamous cell carcinoma: histologic risk assessment, but not margin status, is strongly predictive of local disease-free and overall survival. Am J Surg Pathol. 2005;29:167–78.

    Article  PubMed  Google Scholar 

  3. Yu P, Fu YX. Tumor-infiltrating T lymphocytes: friends or foes? Lab Invest. 2006;86:231–45.

    Article  PubMed  CAS  Google Scholar 

  4. Clemente CG, Mihm MC Jr, Bufalino R, Zurrida S, Collini P, Cascinelli N. Prognostic value of tumor infiltrating lymphocytes in the vertical growth phase of primary cutaneous melanoma. Cancer. 1996;77:1303–10.

    Article  PubMed  CAS  Google Scholar 

  5. Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pagès C, Tosolini M, Camus M, Berger A, Wind P, Zinzindohoué F, Bruneval P, Cugnenc PH, Trajanoski Z, Fridman WH, Pagès F. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science. 2006;313:1960–4.

    Article  PubMed  CAS  Google Scholar 

  6. Piersma SJ, Jordanova ES, van Poelgeest MI, Kwappenberg KM, van der Hulst JM, Drijfhout JW, Melief CJ, Kenter GG, Fleuren GJ, Offringa R, van der Burg SH. High number of intraepithelial CD8+ tumor-infiltrating lymphocytes is associated with the absence of lymph node metastases in patients with large early-stage cervical cancer. Cancer Res. 2007;67:354–61.

    Article  PubMed  CAS  Google Scholar 

  7. Verastegui E, Morales R, Barrera JL, Müeller A, Guzman B, Meneses A, Alfaro G. Immunological approach in the evaluation of regional lymph nodes of patients with squamous cell carcinoma of the head and neck. Clin Immunol. 2002;102:37–47.

    Article  PubMed  Google Scholar 

  8. Zancope E, Costa NL, Junqueira-Kipnis AP, Valadares MC, Silva TA, Leles CR, Mendonça EF, Batista AC. Differential infiltration of CD8+ and NK cells in lip and oral cavity squamous cell carcinoma. J Oral Pathol Med. 2010;39:162–7.

    Article  PubMed  CAS  Google Scholar 

  9. Katou F, Ohtani H, Watanabe Y, Nakayama T, Yoshie O, Hashimoto K. Differing phenotypes between intraepithelial and stromal lymphocytes in early-stage tongue cancer. Cancer Res. 2007;67:11195–201.

    Article  PubMed  CAS  Google Scholar 

  10. Watanabe Y, Katou F, Ohtani H, Nakayama T, Yoshie O, Hashimoto K. Tumor-infiltrating lymphocytes, particularly the balance between CD8(+) T cells and CCR4(+) regulatory T cells, affect the survival of patients with oral squamous cell carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010;109:744–52.

    Article  PubMed  Google Scholar 

  11. Baatar D, Olkhanud P, Sumitomo K, Taub D, Gress R, Biragyn A. Human peripheral blood T regulatory cells (Tregs), functionally primed CCR4+ Tregs and unprimed CCR4- Tregs, regulate effector T cells using FasL. J Immunol. 2007;178:4891–900.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Departments of Pathology, Einstein/Montefiore Head and Neck Research Group, Bronx, NY, USA

    Sara Maleki, Christian Keller, Janice Diaz, Jason Moss, Michael B. Prystowsky & Fernando Macian

  2. Epidemiology and Population Health, Einstein/Montefiore Head and Neck Research Group, Bronx, NY, USA

    Nicolas F. Schlecht

  3. Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA

    Margaret Brandwein-Gensler

Authors
  1. Sara Maleki
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  2. Nicolas F. Schlecht
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  3. Christian Keller
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  4. Janice Diaz
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  5. Jason Moss
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  6. Michael B. Prystowsky
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  7. Fernando Macian
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  8. Margaret Brandwein-Gensler
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Correspondence to Margaret Brandwein-Gensler.

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Maleki, S., Schlecht, N.F., Keller, C. et al. Lymphocytic Host Response to Oral Squamous Cell Carcinoma: An Adaptive T-Cell Response at the Tumor Interface. Head and Neck Pathol 5, 117–122 (2011). https://doi.org/10.1007/s12105-011-0247-1

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  • DOI: https://doi.org/10.1007/s12105-011-0247-1

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