Changes and prognostic values of tumor-infiltrating lymphocyte subsets after primary systemic therapy in breast cancer

• Published in: PloS one 2020-05, Vol.15 (5), p.e0233037-e0233037
• Main Authors: Ahn, Soomin, Chung, Yul Ri, Seo, An Na, Kim, Milim, Woo, Ji Won, Park, So Yeon
• Format: Article
• Language: English
• Subjects: Analysis; Anthracycline; Anthracyclines; Biology and life sciences; Biomarkers; Biopsy; Breast cancer; Cancer research; Cancer therapies; Cancer treatment; Care and treatment; CD4 antigen; CD8 antigen; Chemotherapy; Cloning; Correlation analysis; Diseases; Foxp3 protein; Gene amplification; Health aspects; Health services; Hospitals; Infiltration; Levels; Lymphocytes; Medical prognosis; Medical records; Medical schools; Medicine; Medicine and health sciences; Metastases; Pathology; Patients; Prognosis; Research and Analysis Methods; Studies; Subgroups; Survival; Taxane; Taxanes; Tumor markers; Tumors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0233037

Tumor-infiltrating lymphocyte (TIL) levels have prognostic and predictive values in treatment-naïve breast cancers. However, there have been controversies regarding TIL subset changes and their clinical implications in post-treatment breast cancers. This study aimed to explore change and prognostic significance of TIL subset infiltration after primary systemic therapy (PST) in breast cancer. One-hundred-fifty-five patients who had residual disease after anthracycline- or anthracycline plus taxane-based PST were included. The quantities of intratumoral and stromal TIL subsets (CD8+, CD4+, and FOXP3+ TILs) in pre- and post-PST breast cancer samples, as well as changes between them, were analyzed along with their correlations with clinicopathologic features and outcome of patients. As a whole, intratumoral CD8+ and CD4+ TILs increased after PST while stromal TILs decreased. Both intratumoral and stromal FOXP3+ TILs decreased after PST. The chemo-sensitive group [residual cancer burden (RCB) class I and II] showed the same pattern of change in intratumoral CD8+ TILs as the whole group, whereas the chemo-resistant group (RCB class III) showed no significant change in intratumoral CD8+ TIL infiltration after PST. Survival analyses for each TIL subset as well as their ratios revealed that high levels of intratumoral, stromal, and total CD8+ TIL infiltration after PST were independent predictors of longer patient survival. In subgroup analyses, CD8+ TIL infiltration after PST revealed prognostic significance in the chemo-resistant group but not in the chemo-sensitive group. In conclusion, infiltration of CD8+, CD4+, and FOXP3+ TIL changed after PST in the intratumoral and stromal compartments. Especially, increase of intratumoral CD8+ TILs was associated with chemo-responsiveness. Moreover, CD8+ TIL status in residual tumors after PST may be used as a potential prognostic marker in breast cancer patients who receive PST and provide additional prognostic information to chemo-resistant group.