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

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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-017-0884-8) contains supplementary material, which is available to authorized users.

Concordance of PD‐L1 expression in matched urothelial bladder cancer specimens

“…Discordance in PD‐L1 expression occurred more frequently in patients who had received neoadjuvant therapy, and was associated predominantly with positive PD‐L1 assay in TURB and negative assay at matched cystectomy. The effect of neoadjuvant therapy on PD‐L1 expression might be due to immune suppressive effects of chemotherapy, which has also been observed in breast and non‐small‐cell lung cancer …”

“…The effect of neoadjuvant therapy on PD-L1 expression might be due to immune suppressive effects of chemotherapy, which has also been observed in breast and non-small-cell lung cancer. 9,10 Two recent studies investigated the concordance of different PD-L1 assays in urothelial cancer tissue microarrays, and found PD-L1 expression in 12-29% of samples. 11,12 Tretiakova et al found concordant PD-L1 assay outcome in matched primary urothelial carcinoma and lymph node metastasis in 90%.…”

The combined presence of CD20 + B cells and PD-L1 + tumor-infiltrating lymphocytes in inflammatory breast cancer is prognostic of improved patient outcome

“…The positive prognostic synergy observed in IBC tumors with both CD20 + TILs and PD-L1 + TILs might be the result of cooperation between the cellular and humoral immune responses. While cellular injury and immunogenic cell death induced by chemotherapy can lead to formation of new immunogenic epitopes, chemokine and cytokine secretion, antigen cross-presentation, activation of dendritic cells, and induction of tumor-specific cytotoxic T cells (cellular response) [31], the presence of B cells might enhance such T cell responses by producing antibodies against breast tumor antigens, stimulating cytokine and chemokine secretion, serving as local antigen-presenting cells, and organizing the formation of tertiary lymphoid structures that sustain long-term immunity (humoral response) [32]. As immunotherapy for breast cancer advances, it will be important to evaluate B cell presence, antigen specificity, and activity to determine the extent of B cell modulation and its relationship to patient response.…”

EUS fine-needle pancreatic core biopsy can determine eligibility for tumor-agnostic immunotherapy

“…MMR and PD-L1 status may be influenced by prior neoadjuvant or adjuvant therapy as has been observed in both breast and colon cancer analyses 16 17 . Therefore, for primary pancreatic masses to include PDAC, it may be more desirable to perform such analysis on treatment-naïve specimens for which EUS-FNB is ideally suited to establish the molecular signature.…”