Abstract
BackgroundThe 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.MethodsUsing 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.ResultsOf 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.ConclusionsIncrease 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.
Highlights
The effects of neoadjuvant chemotherapy on immune markers remain largely unknown
The median difference of absolute Tumor infiltrating lymphocyte (TIL) (ΔTIL) count in pre-treatment compared to posttreatment specimens was 5%, indicating an overall increase in TILs in residual disease samples compared to baseline
We have shown in patients who did not achieve Pathologic complete response (pCR) following neoadjuvant chemotherapy that even minor changes in TIL counts can provide hints for a better outcome
Summary
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. Pathologic complete response (pCR) predicts excellent survival while residual disease (RD) is associated with higher but variable risk of Several preclinical studies have suggested that cytotoxic agents partly exert their anti-tumor activity by induction of an anti-tumor immune response aimed at cells injured by chemotherapy. Recent studies on breast cancer patients have suggested that cytotoxic agents, including anthracyclines and taxanes, can induce a tumor-specific immune response, and that exposure to such drugs leads to accumulation of lymphocytes in the tumor bed [7,8,9]. High TIL count in residual disease is associated with better survival [9,10,11]
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