TY - JOUR
T1 - Effect of neoadjuvant chemotherapy on tumor-infiltrating lymphocytes and PD-L1 expression in breast cancer and its clinical significance
AU - Pelekanou, Vasiliki
AU - Carvajal-Hausdorf, Daniel E.
AU - Altan, Mehmet
AU - Wasserman, Brad
AU - Carvajal-Hausdorf, Cristobal
AU - Wimberly, Hallie
AU - Brown, Jason
AU - Lannin, Donald
AU - Pusztai, Lajos
AU - Rimm, David L.
N1 - Funding Information:
This work was supported by the Breast Cancer Research Foundation in grants to DLR and LP, by Susan G. Komen to LP, and by funding from Gilead Sciences to DLR.
Publisher Copyright:
© 2017 The Author(s).
PY - 2017/8/7
Y1 - 2017/8/7
N2 - 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.
AB - 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.
KW - Breast cancer
KW - Neoadjuvant treatment
KW - Programmed death ligand 1
KW - Tumor infiltrating lymphocytes
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U2 - 10.1186/s13058-017-0884-8
DO - 10.1186/s13058-017-0884-8
M3 - Article
C2 - 28784153
AN - SCOPUS:85027151514
SN - 1465-5411
VL - 19
JO - Breast Cancer Research
JF - Breast Cancer Research
IS - 1
M1 - 91
ER -