Multiplexed immunohistochemical analysis of the immune microenvironment of biliary tract cancers pre- & post-neoadjuvant chemotherapy: case series.

Background

Neoadjuvant chemotherapy (NACT) is increasingly being used in the management of locally advanced biliary tract cancer (BTC). The evidence suggests a contributing role of tumor infiltrating immune cells in the prognosis and response. We set out to characterize immune modulation of tumor immune microenvironment in BTC following NACT.

Case Description

Patients with BTC who underwent diagnostic biopsy, then NACT then resection between 2014-2018 were identified. Multiplexed immunohistochemical consecutive staining on single slide (MICSSS) analysis was performed with a series of immune markers to characterize T-cells, immune checkpoints etc. on pre- & post-NACT tumor tissue. Density was calculated for each marker. The final analysis included five patients. Median age was 48 (range, 41-56) years, with 4 female, 4 intrahepatic cholangiocarcinoma and 1 gallbladder. All patients received gemcitabine/cisplatin as NACT (median of 5 cycles). Median time from diagnosis to surgery was 4.3 (range, 1.4-7.8) months. All patients were mismatch repair proficient (pMMR). NACT on average produced a depletion of all immune markers. Given small sample size, each patient was considered their own control and changes in mean cell densities post-NACT were calculated. Patient #2 with a 40-fold increase in PD-L1 expression & 5-fold decrease in CD8:FOXP3 ratio after NACT notably had the shortest disease-free interval (DFI). Patient #3 with the longest DFI had the largest increase in CD8:FOXP3 by about 8-fold with a decrease in PD-L1.

Conclusions

Preliminary results suggest NACT may differentially modulate various compartments of the immune tumor contexture despite overall cell depletion. Future studies should focus on strategies to expand immune modulation of tumor microenvironment, including immune-oncology agents to augment the effects of chemotherapy.

Informations de copyright

2024 Annals of Translational Medicine. All rights reserved.

Déclaration de conflit d'intérêts

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-23-1928/coif). G.A. is currently working as a Director at Merck & Co., Inc. in the Department of Molecular Pathology, Translational Molecular Biomarkers Kenilworth, New Jersey, United States and also owns Merck & Co., Inc. stocks. M.E.S. reports consulting or advisory role in Eisai and Genentech; research funding from Bristol-Myers Squibb. D.J.C. reports consulting or advisory role in Taiho Oncology; research funding from Bristol-Myers Squibb, Eisai, and Merck (all payments were made to institution). S.G. reports research funding from Boehringer Ingelheim, Bristol-Myers Squibb/Medarex, Celgene, EMD Serono, Janssen, Regeneron and Takeda (all payments were made to institution); patents, royalties, other intellectual property: patent on GM-CSF autoantibodies; patent on Multiplex Immunohistochemistry with Chromogen Staining on a Single Slide (MICSSS); patents related to immune composition of NY-E; patents related to immune composition of NY-ESO-1 and peptides, SO-1 and peptides; provisional patent on ELLA cytokines. S.P. reports that this work was funded by the Cholangiocarcinoma Foundation, and consulting or advisory role in Tesaro. The other authors have no conflicts of interest to declare.