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Tumor-infiltrating lymphocytes predict response to chemotherapy in patients with advance non-small cell lung cancer

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Abstract

Accumulating preclinical evidence suggests that anticancer immune responses contribute to the success of chemotherapy. The predictive significance of tumor-infiltrating lymphocytes (TILs) for response to neoadjuvant chemotherapy in non-small cell lung cancer (NSCLC) remains unknown. The aim of this study was to investigate the prognostic and predictive value of TIL subtypes in patients with advanced NSCLC treated with platinum-based chemotherapy. In total, 159 patients with stage III and IV NSCLC were retrospectively enrolled. The prevalence of CD3+, CD4+, CD8+ and Foxp3+ TILs was assessed by immunohistochemistry in tumor tissue obtained before chemotherapy. The density of TILs subgroups was treated as dichotomous variables using the median values as cutoff. Survival curves were estimated by the Kaplan–Meier method, and differences in overall survival between groups were determined using the Log-rank test. Prognostic effects of TIL subsets density were evaluated by Cox regression analysis. The presence of CD3+, CD4+, CD8+, and FOXP3+ TILs was not correlated with any clinicopathological features. Neither the prevalence of TILs nor combined analysis displayed obvious prognostic performances for overall survival in Cox regression model. Instead, higher FOXP3+/CD8+ ratio in tumor sites was an independent factor for poor response to platinum-based chemotherapy in overall cohort. These findings suggest that immunological CD8+ and FOXP3+Tregs cell infiltrate within tumor environment is predictive of response to platinum-based neoadjuvant chemotherapy in advanced NSCLC patients. The understanding of the clinical relevance of the microenvironmental immunological milieu might provide an important clue for the design of novel strategies in cancer immunotherapy.

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Abbreviations

BC:

Breast cancer

CRC:

Colorectal cancer

CTL:

Cytotoxic T lymphocytes

FOXP3:

Forkhead box P3

HPF:

High power field

IHC:

Immunohistochemistry

NSCLC:

Non-small cell lung cancer

OC:

Ovarian cancer

OS:

Overall survival

TIL:

Tumor-infiltrating lymphocytes

Treg:

Regulatory T lymphocytes

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Acknowledgments

This work was supported by grants from the National Science Foundation of China (grants 81000986).

Conflict of interest

All other authors indicated no potential conflict of interest.

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Authors and Affiliations

  1. Institute of Respiratory Diseases of Sun Yat-Sen University, Division of Pulmonary and Critical Care, Department of Internal Medicine, The Third Affiliated Hospital of Sun Yat-Sen University, No. 600 Tianhe Street, Guangzhou, 510630, China

    Hui Liu, Tiantuo Zhang, Hongtao Li, Jing Huang & Benquan Wu

  2. Department of Otolaryngology, Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, No. 600 Tianhe Street, Guangzhou, 510630, China

    Jin Ye

  3. Department of Thoracic Surgery, Cancer Center, Sun Yat-Sen University, 651 Dongfeng dong Street, Guangzhou, 510060, China

    Xiaodong Li

  4. Division of Pulmonary and Critical Care, Department of Internal Medicine, The First Affiliated Hospital of Sun Yat-Sen University, No. 58 Zhongshan Er Street, Guangzhou, 510080, China

    Xubing Huang

  5. Department of Pathology, Cancer Center, Sun Yat-Sen University, No. 651 Dongfeng dong Street, Guangzhou, 510630, China

    Jinghui Hou

Authors
  1. Hui Liu
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  2. Tiantuo Zhang
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  9. Jinghui Hou
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Correspondence to Tiantuo Zhang.

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Liu, H., Zhang, T., Ye, J. et al. Tumor-infiltrating lymphocytes predict response to chemotherapy in patients with advance non-small cell lung cancer. Cancer Immunol Immunother 61, 1849–1856 (2012). https://doi.org/10.1007/s00262-012-1231-7

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  • DOI: https://doi.org/10.1007/s00262-012-1231-7

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