Journal Article
. 2014 Oct; 51(1):90-5.
doi: 10.1016/j.oraloncology.2014.09.006.

Tumor infiltrating lymphocytes (TIL) and prognosis in oral cavity squamous carcinoma: a preliminary study

Gregory T Wolf 1 Douglas B Chepeha 2 Emily Bellile 3 Ariane Nguyen 2 Daffyd Thomas 4 Jonathan McHugh 4 University of Michigan Head and Neck SPORE Program  
Affiliations
  • PMID: 25283344
  •     52 References
  •     58 citations

Abstract

Objectives: Tumor infiltrating lymphocytes (TILs) in the microenvironment reflect may tumor biology and predict outcome. We previously demonstrated that infiltrates of CD4, CD8, and FoxP3 positive lymphocytes were associated with HPV-status and survival in oropharyngeal cancers. To determine if TILs were of prognostic importance in oral cancer, TIL levels were evaluated retrospectively in 52 oral cancer patients treated with surgery and correlations with outcome determined.

Methods: Complete TIL and clinical data were available for 39 patients. Levels of CD4, CD8, FoxP3 (Treg), CD68 and NK cells were assessed by immunohistochemistry in tumor cores on a tissue microarray. Associations with clinical variables, tobacco and alcohol use and histologic features were assessed using Spearman correlation coefficient and the non-parametric Kruskal-Wallis testing. Time-to-event outcomes were determined using univariate and multivariate Cox models. Median follow up was 60 months.

Results: The ratio of CD4/CD8 (p=.01) and CD8 infiltrates (p=.05) were associated with tumor recurrence but not overall survival. Lower CD4 infiltrates were associated with alcohol use (p=.005) and poor tumor differentiation (p=.02). Interestingly, higher levels of CD68+ macrophages were found associated with positive nodes (p=.06) and poorer overall survival (p=.07). Overall and DSS survival were significantly shorter for patients with positive nodes, extracapsular spread, or perineural invasion.

Conclusion: Infiltrating immune cell levels in oral cavity cancer appear influenced by health behaviors and tumor characteristics. In contrast to oropharynx cancer, infiltrates of CD68 positive tumor associated macrophages may contribute to metastatic behavior and outcome in advanced oral cavity carcinoma.

Keywords: Oral cavity cancer; Tumor associated macrophage; Tumor infiltrating lymphocytes.

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Muzafar A Macha, Nissar A Wani, +7 authors, Surinder K Batra.
Adv Exp Med Biol, 2020 Jan 01; 1296. PMID: 34185284
Immune landscape and subtypes in primary resectable oral squamous cell carcinoma: prognostic significance and predictive of therapeutic response.
Pengfei Diao, Yue Jiang, +17 authors, Jie Cheng.
J Immunother Cancer, 2021 Jun 17; 9(6). PMID: 34130988    Free PMC article.
Prognostic Relevance of CD4+, CD8+ and FOXP3+ TILs in Oral Squamous Cell Carcinoma and Correlations with PD-L1 and Cancer Stem Cell Markers.
Paloma Lequerica-Fernández, Julián Suárez-Canto, +6 authors, Juan Carlos de Vicente.
Biomedicines, 2021 Jul 03; 9(6). PMID: 34201050    Free PMC article.
Tumor microenvironment is not an 'innocent bystander' in the resistance to treatment of head and neck cancers (Review).
Laura Mazilu, Andra-Iulia Suceveanu, +3 authors, Serban-Mircea Negru.
Exp Ther Med, 2021 Sep 02; 22(4). PMID: 34466142    Free PMC article.
Review.
A TP53 mutation model for the prediction of prognosis and therapeutic responses in head and neck squamous cell carcinoma.
Congyu Shi, Shan Liu, +2 authors, Pan Gao.
BMC Cancer, 2021 Sep 18; 21(1). PMID: 34530752    Free PMC article.
CD68+ Macrophage Infiltration Associates With Poor Outcome of HPV Negative Oral Squamous Carcinoma Patients Receiving Radiation: Poly(I:C) Enhances Radiosensitivity of CAL-27 Cells but Promotes Macrophage Recruitment Through HMGB1.
Dan Ai, Yu Dou, +14 authors, Xun Qu.
Front Oncol, 2021 Sep 28; 11. PMID: 34568076    Free PMC article.
High PD-L1 Expression on Tumor Cells Indicates Worse Overall Survival in Advanced Oral Squamous Cell Carcinomas of the Tongue and the Floor of the Mouth but Not in Other Oral Compartments.
Łukasz Jan Adamski, Anna Starzyńska, +7 authors, Rafał Pęksa.
Biomedicines, 2021 Sep 29; 9(9). PMID: 34572318    Free PMC article.
A Novel Ferroptosis-Related Gene Signature to Predict Prognosis in Patients with Head and Neck Squamous Cell Carcinoma.
Li Xu, Ying-Ying Li, +4 authors, Zhao-Hui Liu.
Dis Markers, 2021 Dec 03; 2021. PMID: 34853622    Free PMC article.