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. 2024 Jun 27;25(13):7070.
doi: 10.3390/ijms25137070.

The Impact of Neoadjuvant Chemotherapy on Ovarian Cancer Tumor Microenvironment: A Systematic Review of the Literature

Giulia Spagnol  1 , Eleonora Ghisoni  2   3   4 , Matteo Morotti  2   3   4 , Orazio De Tommasi  1 , Matteo Marchetti  1 , Sofia Bigardi  1 , Valentina Tuninetti  5 , Giulia Tasca  6 , Marco Noventa  1 , Carlo Saccardi  1 , Roberto Tozzi  1 , Denarda Dangaj Laniti  2   3   4
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The Impact of Neoadjuvant Chemotherapy on Ovarian Cancer Tumor Microenvironment: A Systematic Review of the Literature

Giulia Spagnol et al. Int J Mol Sci. .

Abstract

Immunotherapy, particularly the use of immune checkpoint inhibitors (ICIs), has shown limited efficacy in treating ovarian cancer (OC), possibly due to diverse T cell infiltration patterns in the tumor microenvironment. This review explores how neoadjuvant chemotherapy (NACT) impacts the immune landscape of OC, focusing on tumor-infiltrating lymphocytes (TILs), PD-1/PD-L1 expression, and their clinical implications. A comprehensive literature search across four databases yielded nine relevant studies. These studies evaluated stromal (sTILs) and intra-epithelial (ieTILs) TILs before and after NACT. sTIL responses varied, impacting prognostic outcomes, and ieTILs increased in some patients without clear survival associations. PD-L1 expression after NACT correlated with improved overall survival (OS), and increases in granzyme B+ and PD-1 correlated with longer progression-free survival (PFS). Remarkably, reduced FoxP3+ TILs post-NACT correlated with better prognosis. NACT often increases sTIL/ieTIL and CD8+ subpopulations, but their correlation with improved PFS and OS varies. Upregulation of co-inhibitory molecules, notably PD-L1, suggests an immunosuppressive response to chemotherapy. Ongoing trials exploring neoadjuvant ICIs and chemotherapy offer promise for advancing OC treatment. Standardized measurements assessing TIL density, location, and heterogeneity are crucial for addressing genetic complexity and immunological heterogeneity in OC.

Keywords: NACT; TILs; ovarian cancer.

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Conflict of interest statement

D.D.L. declares receiving funding from Hoffmann-La Roche AG. The funder was not involved in this study nor in its design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication.

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Figure 1
PRISMA flow diagram.
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