Effect of neoadjuvant chemotherapy on tumor-infiltrating lymphocytes and PD-L1 expression in breast cancer and its clinical significance

• Published in: Breast cancer research : BCR Vol. 19; no. 1; p. 91
• Main Authors: Pelekanou, Vasiliki, Carvajal-Hausdorf, Daniel E, Altan, Mehmet, Wasserman, Brad, Carvajal-Hausdorf, Cristobal, Wimberly, Hallie, Brown, Jason, Lannin, Donald, Pusztai, Lajos, Rimm, David L
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 07.08.2017; BioMed Central; BMC
• Subjects: Adjuvant chemotherapy; Apoptosis; Breast cancer; Cancer therapies; Chemotherapy; Clinical significance; Cytotoxicity; Drug therapy; Gene expression; Genetic aspects; Health aspects; Immunofluorescence; L1 protein; Ligands; Lung cancer; Lymphocytes; Medical prognosis; Melanoma; Metastases; Neoadjuvant treatment; Patients; PD-L1 protein; Physiological aspects; Programmed death ligand 1; Studies; Survival; Tumor cells; Tumor infiltrating lymphocytes; United States; Breast cancer; Programmed death ligand 1; Tumor infiltrating lymphocytes; Neoadjuvant treatment
• ISSN: 1465-542X; 1465-5411; 1465-542X
• DOI: 10.1186/s13058-017-0884-8

The effects of neoadjuvant chemotherapy on immune markers remain largely unknown. The specific aim of this study was to assess stromal tumor-infiltrating lymphocytes (TILs) and programmed death ligand 1 (PD-L1) protein expression in a cohort of breast cancer patients treated with neoadjuvant chemotherapy. Using quantitative immunofluorescence, we investigated stromal TILs and PD-L1 protein expression in pre-treatment and residual breast cancer tissue from a Yale Cancer Center patient cohort of 58 patients diagnosed with breast cancer from 2003 to 2009 and treated with neoadjuvant chemotherapy. We compared the TIL count and PD-L1 status in paired pre-treatment and residual cancer tissues and correlated changes and baseline levels with survival. Of the 58 patients, 46 (79.3%) had hormone-positive and 34 (58.6%) had node-positive breast cancer. Eighty-six percent of residual cancer tissues had TIL infiltration and 17% had PD-L1 expression. There was a trend for higher TIL counts in postchemotherapy compared to prechemotherapy samples (p = 0.09). Increase in TIL count was associated with longer 5-year recurrence-free survival (p = 0.02, HR = 3.9, 95% CI = 1.179-15.39). PD-L1 expression (both stromal and tumor cells) was significantly lower in post-treatment samples (p = 0.001). Change in PD-L1 expression after therapy or TILs and PD-L1 expression in the posttreatment samples did not correlate with survival. Increase in stromal TILs in residual cancer compared to pretreatment tissue is associated with improved recurrence-free survival. Despite a trend for increasing TIL counts, PD-L1 expression decreased in residual disease compared to pretreatment samples.