Cancer Immunology, Immunotherapy

, Volume 61, Issue 10, pp 1849–1856 | Cite as

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

  • Hui Liu
  • Tiantuo ZhangEmail author
  • Jin Ye
  • Hongtao Li
  • Jing Huang
  • Xiaodong Li
  • Benquan Wu
  • Xubing Huang
  • Jinghui Hou
Original article


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.


Chemotherapy Cytotoxic T lymphocytes Immunity Prognostic factor Non-small cell lung cancer Tumor-infiltrating lymphocytes 



Breast cancer


Colorectal cancer


Cytotoxic T lymphocytes


Forkhead box P3


High power field




Non-small cell lung cancer


Ovarian cancer


Overall survival


Tumor-infiltrating lymphocytes


Regulatory T lymphocytes



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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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Hui Liu
    • 1
  • Tiantuo Zhang
    • 1
    Email author
  • Jin Ye
    • 2
  • Hongtao Li
    • 1
  • Jing Huang
    • 1
  • Xiaodong Li
    • 3
  • Benquan Wu
    • 1
  • Xubing Huang
    • 4
  • Jinghui Hou
    • 5
  1. 1.Institute of Respiratory Diseases of Sun Yat-Sen University, Division of Pulmonary and Critical Care, Department of Internal MedicineThe Third Affiliated Hospital of Sun Yat-Sen UniversityGuangzhouChina
  2. 2.Department of Otolaryngology, Head and Neck SurgeryThe Third Affiliated Hospital of Sun Yat-Sen UniversityGuangzhouChina
  3. 3.Department of Thoracic Surgery, Cancer CenterSun Yat-Sen UniversityGuangzhouChina
  4. 4.Division of Pulmonary and Critical Care, Department of Internal MedicineThe First Affiliated Hospital of Sun Yat-Sen UniversityGuangzhouChina
  5. 5.Department of Pathology, Cancer CenterSun Yat-Sen UniversityGuangzhouChina

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