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

Pelekanou, Vasiliki; Carvajal-Hausdorf, Daniel E.; Altan, Mehmet; Wasserman, Brad; Carvajal-Hausdorf, Cristobal; Wimberly, Hallie; Brown, Jason; Lannin, Donald; Pusztai, Lajos; Rimm, David L.


Background: 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. Methods: Using quantitative immunofluorescence, we investigated stromal TILs and PD-L1 protein expression in pretreatment 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. Results: 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. Conclusions: 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.

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Título según WOS: ID WOS:000407142600001 Not found in local WOS DB
Título de la Revista: BREAST CANCER RESEARCH
Volumen: 19
Editorial: BMC
Fecha de publicación: 2017


Notas: ISI