The Impact of Neoadjuvant Chemotherapy on Ovarian Cancer Tumor Microenvironment: A Systematic Review of the Literature
Abstract
:1. Introduction
2. Methods
2.1. Information Sources and Search Strategies
2.2. Eligibility Criteria
- Type of study: case-control studies, cohort studies, or case series.
- Period of publication: no restriction.
- Language: only English-language studies were included.
- Data search: January 2003–December 2023.
- Participants: women with ovarian cancer who underwent NACT with available samples before and after chemotherapy, as well as immune cell infiltration evaluation.
- Comparators: (i) sTILs and ieTILs before and after NACT; (ii) PD-1, PD-L1 expression and other immune cell populations before and after NACT.
- Outcomes: prognostic impact of sTILs and ieTILs, PD-1/PD-L1, and other immune cell populations before and after NACT in terms of PFS and OS.
2.3. Study Selection and Data Extraction
3. Results and Discussion
3.1. Study Selection
Study and Patient Characteristics Overview
3.2. Tumor-Infiltrating Lymphocytes (TILs)
3.2.1. Stromal TILs (sTILs)
3.2.2. Intraepithelial TILs (ieTILs)
3.3. PD-1, PD-L1 Expression and Other Cytokine Expression
3.4. Discussion
Combination of Immune Checkpoint Inhibitors and Chemotherapy
4. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Study Design | Number of Patients | Number of Patients with Paired Pre- and Post-NACT | Histotype | Site of Origin | TILs Assessment | Type of CHT | Number of Cycles | FU | |
---|---|---|---|---|---|---|---|---|---|
Polcher et al. 2010 [23] | Prospective | 93 | 30 | Serous/serous-papillary High-grade endometrioid (EC) | Intraperitoneal biopsies | Hematoxylin staining (HS) Immunohistochemistry (IHC) | Platinum-/ taxane-based NAC | 3 cycles | 24 months |
Bohm et al. 2016 [24] | Prospective | 60 | 54 | HGSC | Omental biopsies and plasma samples | IHC, flow cytometry (FC), electrochemiluminescence assays, and RNA sequencing (RS) | Taxane/platinum combinations | 3 or >4 | NA |
Lo et al. 2016 [25] | Retrospective | 150 | 26 (in 18 patients, paired anatomic extra-pelvic biopsies were available) | HGSC | Omentum, pelvic site, uterus, colon, abdomen, cul-de-sac (paired only extra-pelvic biopsies) | IHC (Aperio, Pannoramic MIDI, Vectra) | Platinum-/ taxane-based NAC | A mean of 4 cycles | NA |
Mesnage et al. 2016 [26] | Retrospective | 150 | 83 | High-grade serous (HGSC), EC, clear cell (CC), low-grade serous (LGSC), mucinous carcinoma (MC) | NA | Hematoxylin and eosin staining (HES) IHC | Carboplatin and paclitaxel | Average 4 cycles | 52 months |
Kim et al. 2018 [27] | Retrospective | 266 | 76 | HGSC | Omental biopsies | HES, IHC (Ventana XT automated stainer) | Taxane/platinum combinations | A median of 3 cycles (range, 2–6 cycles) | Median: 30 months |
Chen et al. 2020 [28] | Retrospective | 189 | 15 | HGSC, CC, EC, MC | NA | HES, IHC (Aperio ScanScope AT Turbo scanner) | Platinum-based treatment | N/A | 37 months |
Leary et al. 2020 [29] | Retrospective | 150 | 53 | HGSC, EC, CC, other high-grade, LGSC, MC | NA | HES, IHC | Platinum and paclitaxel | Mean number of cycles: 4 | Median: 80 months |
Félix Blanc-Durand et al. 2020 [30] | Retrospective | 98 | 63 | HGSC, LGSC, mixed, poorly differentiated, EC, CC, MC | NA | HES, IHC (Ventana XT automated stainer) | Platinum-based treatment | N/A | N/A |
Lee et al. 2022 [31] | Retrospective | 147 | 147 | HGSC | NA | HES, IHC (Ventana XT automated stainer), whole-transcriptome sequencing (WTS) | Platinum-based chemotherapy | Median of 3 cycles (range, 3–4 cycles) | Median: 28.2 months |
Stromal | Prognostic Association Pre-NACT | Prognostic Association Post-NACT | Study |
---|---|---|---|
TILs | PFS increase with ↑ | PFS increase with ↑ | Mesnage et al. [26] |
None | None | Kim et al. [27] | |
PFS increase with
↑
OS increase with ↑ | None | Lee et al. [31] | |
CD8+ | None | None | Leary et al. [29] |
PFS increase with
↑
OS increase with ↑ | None | Lee et al. [31] | |
CD3+ | None | None | Leary et al. [29] |
CD4+ | None | None | Leary et al. [29] |
None | None | Bohm et al. [24] | |
Foxp3+ | None |
PFS increase with
↑
OS none | Leary et al. [29] |
PFS increase with
↑
OS increase with ↑ | None | Lee et al. [31] |
Tumor | Prognostic Association Pre-NACT | Prognostic Association Post-NACT | Study |
---|---|---|---|
TILs | None | None | Mesnage et al. [26] |
CD8+ | None | None | Polcher et al. [23] |
None | None | Lo et al. [25] | |
None | None | Leary et al. [29] | |
CD3+ | None | None | Lo et al. [25] |
None | None | Leary et al. [29] | |
CD4+ | None | None | Polcher et al. [23] |
None | None | Leary et al. [29] | |
Foxp3+ | None | PFS increase with ↓ OS increase with ↓ | Polcher et al. [23] |
None | None | Lo et al. [25] | |
None | None | Leary et al. [29] | |
CD20+ | None | PFS none OS increase with ↑ | Lo et al. [25] |
CD8+/Foxp3+ | None | None | Polcher et al. [23] |
CD8+/CD4+ | None | PFS none OS increase with ↑ | Polcher et al. [23] |
Prognostic Association Pre-NACT | Prognostic Association Post-NACT | Study | |
---|---|---|---|
Granzime B+ | None | PFS increase with ↑ OS none | Polcher et al. [23] |
GranzymeB/Foxp3 | None | PFS increase with ↑ OS none | Polcher et al. [23] |
PD-L1 | None | None | Mesnage et al. [26] |
None | None | Kim et al. [27] | |
None | None | Bohm et al. [24] | |
None | None | Lo et al. [25] | |
None | PFS increase with ↑ OS increase with ↑ | Chen et al. [28] | |
None | None | Félix Blanc-Durand et al. [30] | |
PFS increase with ↑ OS increase with ↑ | None | Lee et al. [31] | |
PD-1 | None | None | Lo et al. [25] |
IDO-1 | None | None | Félix Blanc-Durand et al. [30] |
TIM3+ | None | None | Félix Blanc-Durand et al. [30] |
LAG3+ | None | None | Félix Blanc-Durand et al. [30] |
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Spagnol, G.; Ghisoni, E.; Morotti, M.; De Tommasi, O.; Marchetti, M.; Bigardi, S.; Tuninetti, V.; Tasca, G.; Noventa, M.; Saccardi, C.; et al. The Impact of Neoadjuvant Chemotherapy on Ovarian Cancer Tumor Microenvironment: A Systematic Review of the Literature. Int. J. Mol. Sci. 2024, 25, 7070. https://doi.org/10.3390/ijms25137070
Spagnol G, Ghisoni E, Morotti M, De Tommasi O, Marchetti M, Bigardi S, Tuninetti V, Tasca G, Noventa M, Saccardi C, et al. The Impact of Neoadjuvant Chemotherapy on Ovarian Cancer Tumor Microenvironment: A Systematic Review of the Literature. International Journal of Molecular Sciences. 2024; 25(13):7070. https://doi.org/10.3390/ijms25137070
Chicago/Turabian StyleSpagnol, Giulia, Eleonora Ghisoni, Matteo Morotti, Orazio De Tommasi, Matteo Marchetti, Sofia Bigardi, Valentina Tuninetti, Giulia Tasca, Marco Noventa, Carlo Saccardi, and et al. 2024. "The Impact of Neoadjuvant Chemotherapy on Ovarian Cancer Tumor Microenvironment: A Systematic Review of the Literature" International Journal of Molecular Sciences 25, no. 13: 7070. https://doi.org/10.3390/ijms25137070