Clinical Validity and Utility of Tumor-Infiltrating Lymphocytes in Routine Clinical Practice for Breast Cancer Patients: Current and Future Directions.

Lironne Wein,Stephen J Luen,Sherene Loi,Roberto Salgado,Balaji Virassamy,Peter Savas

doi:10.3389/fonc.2017.00156

Abstract

The interest in tumor-infiltrating lymphocytes (TILs) as a prognostic biomarker in breast cancer has grown in recent years. Biomarkers must undergo comprehensive evaluation in terms of analytical validity, clinical validity and clinical utility before they can be accepted as part of clinical practice. The International Immuno-Oncology Biomarker Working Group has developed a practice guideline on scoring TILs in breast cancer in order to standardize TIL assessment. The prognostic value of TILs as a biomarker in early-stage breast cancer has been established by assessing tumor samples in thousands of patients from large prospective clinical trials of adjuvant therapy. There is a strong linear relationship between increase in TILs and improved disease-free survival for triple-negative and HER2-positive disease. Higher levels of TILs have also been associated with increased rates of pathological complete response to neoadjuvant therapy. TILs have potential clinical utility in breast cancer in a number of areas. These include prediction of responders to immune checkpoint blockade, identification of primary HER2-positive and triple-negative patients who have excellent prognoses and may thus be appropriate for treatment de-escalation, and potentially incorporation into a neoadjuvant endpoint which may be a better surrogate maker for drug development.

Highlights

It has been well established that the immune system plays a crucial role in host defense against tumor progression
The GeparSixto trial investigated the effect of adding carboplatin to an anthracycline-plus-taxane combination in triplenegative and HER2-positive tumors. Evaluation of these tumors demonstrated that increased levels of stromal Tumor-infiltrating lymphocytes (TILs) and lymphocyte predominant breast cancer (LPBC) were associated with higher rates of pathological complete response (pCR) [19]. pCR rates in LPBC tumors were significantly higher with the addition of carboplatin, with carboplatin increasing the odds of pCR 3.71-fold in LPBC tumors compared with a 1.01-fold increase in non-LPBCs
It is clear that higher levels of TILs are associated with improved prognosis in early and advanced stage TNBC and HER2-positive breast cancer, as well as a higher probability of achieving pCR in the neoadjuvant setting

Summary

INTRODUCTION

It has been well established that the immune system plays a crucial role in host defense against tumor progression. Tumor-infiltrating lymphocytes (TILs) have provided insight into the immunogenicity of breast tumors and have been shown to be useful as a prognostic biomarker in early-stage triple-negative and HER2-positive breast cancer

BACKGROUND

Findings

CONCLUSION