Dynamics of the Tumor Immune Microenvironment during Neoadjuvant Chemotherapy of High-Grade Serous Ovarian Cancer

Lee, Yong Jae; Woo, Ha Young; Kim, Yoo-Na; Park, Junsik; Nam, Eun Ji; Kim, Sang Wun; Kim, Sung Hoon; Kim, Young-Tae; Park, Eunhyang; Joung, Je-Gun

doi:10.3390/cancers14092308

Cited by 17 publications

(11 citation statements)

References 39 publications

(50 reference statements)

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“…Previous studies have shown the effect of chemotherapeutic regimens on tumor immune microenvironment, including an increase in infiltration of CD8 + T cells, CD3 + T cells, CD20 + B cells, and PD-1 + cells ( 13 – 15 , 19 , 20 ). Regulation of tumor-promoting immune suppressors and immune effectors of the immune system might result in the enhanced antitumor activity of immunotherapies.…”

Section: Discussionmentioning

confidence: 99%

Tumor immune microenvironment changes are associated with response to neoadjuvant chemotherapy and long-term survival benefits in advanced epithelial ovarian cancer: A pilot study

Cao

Hua²,

Li³

et al. 2023

Front. Immunol.

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Little is known about the association between efficacy of neoadjuvant chemotherapy (NACT)/survival and the dynamic change of tumor immune environment (TIME) during treatment in epithelial ovarian cancer (EOC). This study investigated the TIME landscape of treatment-naive EOC tumors using multiplex immunofluorescence and associated the TIME before and after platinum-based NACT with treatment efficacy and prognosis in 33 patients with advanced EOC. NACT significantly increased the density of CD8+ T cells (P = 0.033), CD20+ B cells (P = 0.023), CD56 NK cells (P = 0.041), PD-1+ cells (P = 0.042), and PD-L1+CD68+ macrophages (P = 0.005) in the tissue specimens. Response to NACT was evaluated using CA125 response and chemotherapy response score (CRS). Compared with the non-responders, the responders displayed a larger proportion of tumors showing increase in the infiltration of CD20+ cells (P = 0.046) and in the M1/M2 ratio (P = 0.038) as well as fewer tumors showing increase in the infiltration of CD56bright cells (P = 0.041). No association was found between pre-NACT TIME and response to NACT. Density of pre-NACT CD8+ cells was positively associated with longer progression-free survival (PFS) (P = 0.011) and overall survival (OS) (P = 0.048). Post-NACT CD20+ and CD163+ macrophages (M2) infiltrates were associated with prolonged (P = 0.005) and shortened PFS (P = 0.021), respectively. Increase in the density of CD4+ T cells was predictive for longer PFS (P = 0.022) and OS (P = 0.023). In the multivariate analysis, high density of CD8+ cells pre-NACT (P = 0.042) were independently associated with improved OS.

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Section: Discussionmentioning

confidence: 99%

Tumor immune microenvironment changes are associated with response to neoadjuvant chemotherapy and long-term survival benefits in advanced epithelial ovarian cancer: A pilot study

Cao

Hua²,

Li³

et al. 2023

Front. Immunol.

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“…Maximal cytoreductive surgery with platinum-based chemotherapy is the standard treatment modality for advanced-stage ovarian cancer . However, despite achieving complete remission after primary treatment, 60% to 80% of patients with advanced-stage ovarian cancer experience relapse . Several new combinations with platinum-based chemotherapy, including targeted agents, antiangiogenic agents, immunotherapy, and intraperitoneal chemotherapy, have been developed to improve survival outcomes …”

Section: Introductionmentioning

confidence: 99%

“…2,3 However, despite achieving complete remission after primary treatment, 60% to 80% of patients with advanced-stage ovarian cancer experience relapse. 4,5 Several new combinations with platinum-based chemotherapy, including targeted agents, antiangiogenic agents, immunotherapy, and intraperitoneal chemotherapy, have been developed to improve survival outcomes. 6 Hyperthermic intraperitoneal chemotherapy (HIPEC) combines intraperitoneal chemotherapy with hyperthermia and maintains a high chemotherapeutic drug concentration in tumor cells and reduces the adverse effects of intraperitoneal catheter-related complications.…”

mentioning

confidence: 99%

Hyperthermic Intraperitoneal Chemotherapy After Interval Cytoreductive Surgery for Patients With Advanced-Stage Ovarian Cancer Who Had Received Neoadjuvant Chemotherapy

Lee,

Son

et al. 2023

JAMA Surg

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ImportanceHyperthermic intraperitoneal chemotherapy (HIPEC) followed by interval cytoreductive surgery (ICS) has shown survival benefits for patients with advanced-stage ovarian cancer. However, there is still a lack of consensus regarding the integration of HIPEC into clinical practice.ObjectiveTo evaluate the safety and effectiveness of ICS with HIPEC compared with ICS alone in clinical practice for patients with advanced-stage ovarian cancer.Design, Setting, and ParticipantsThis prospective, multicenter, comparative effectiveness cohort study enrolled 205 patients with stage III or IV ovarian cancer who had received at least 3 cycles of neoadjuvant chemotherapy followed by ICS with HIPEC or ICS without HIPEC at 7 Korean Gynecologic Oncology Group institutions between September 1, 2017, and April 22, 2022. Nine patients were excluded because they did not meet the inclusion criteria.ExposuresNeoadjuvant chemotherapy followed by ICS with HIPEC or ICS without HIPEC.Main Outcomes and MeasuresThe primary end point was progression-free survival (PFS). Overall survival (OS) and the safety profile were the key secondary end points.ResultsThis study included 196 patients (median age, 58.0 years [range, 38-82 years]), of whom 109 underwent ICS with HIPEC and 87 underwent ICS without HIPEC. The median duration of follow-up was 28.2 months (range, 3.5-58.6 months). Disease recurrence occurred in 128 patients (65.3%), and 30 patients (15.3%) died. Interval cytoreductive surgery with HIPEC was associated with a significant improvement in median PFS compared with ICS without HIPEC (22.9 months [95% CI, 3.5-58.6 months] vs 14.2 months [95% CI, 4.0-56.2 months]; P = .005) and median OS (not reached [95% CI, 3.5 months to not reached] vs 53.0 [95% CI, 4.6-56.2 months]; P = .002). The frequency of grade 3 or 4 postoperative complications was similar in both groups (ICS with HIPEC, 3 of 109 [2.8%] vs ICS without HIPEC, 3 of 87 [3.4%]; P &gt; .99). Among patients with recurrence, the frequency of peritoneal recurrence was lower in the ICS with HIPEC group than in the ICS without HIPEC group (21 of 64 [32.8%] vs 41 of 64 [64.1%]; P = .001).Conclusions and RelevanceThis study suggests that ICS in conjunction with HIPEC was associated with longer PFS and OS than ICS without HIPEC for patients with advanced-stage ovarian cancer and was not associated with higher rates of postoperative complications. The lower rate of peritoneal recurrence after HIPEC may be associated with improved OS.

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“…NACT has been reported to induce changes in immune regulatory signals as well as reprogramming the tumour immune microenvironment 17,18,19 . In our study, NACT resulted in a significant change in the I-O gene expression signatures associated with avoiding immune destruction and tumour promoting inflammation signatures.…”

Section: Immuno-oncology (I-o) and Inflammation Related Gene Signatur...mentioning

confidence: 99%

Temporal and disease-site specific transcriptional and phenotypic changes in response to neoadjuvant chemotherapy in high-grade serous ovarian cancers

Saha¹,

Gentles

Howarth

et al. 2023

Preprint

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Neoadjuvant chemotherapy (NACT) has been known to induce genomic and transcriptomic alterations within tumours. Here, using transcriptome profiling along with histological analysis of pre and post NACT, we show temporal and disease site-specific differences (omentum, ovary and other sites) in high grade serous ovarian cancer (HGSOC) and their association with progression free and overall survival. We observed a significant reduction in genome instability signature score following NACT irrespective of disease site, which correlated with homologous recombination repair (HRR) function measured by RAD51 foci formation. However, increase in immuno-oncology and inflammation signatures was only observed in the omentum and not in the ovary post-NACT. DNA damage immune response (DDIR) along with HRR function were strongly associated with CD8+ T-cell infiltration within tumours. Our study provides transcriptomic and phenotypic data highlighting the heterogeneity in HGSOCs during the course of treatment and indicating how the tumour evolves in response to NACT.

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Dynamics of the Tumor Immune Microenvironment during Neoadjuvant Chemotherapy of High-Grade Serous Ovarian Cancer

Cited by 17 publications

References 39 publications

Tumor immune microenvironment changes are associated with response to neoadjuvant chemotherapy and long-term survival benefits in advanced epithelial ovarian cancer: A pilot study

Tumor immune microenvironment changes are associated with response to neoadjuvant chemotherapy and long-term survival benefits in advanced epithelial ovarian cancer: A pilot study

Hyperthermic Intraperitoneal Chemotherapy After Interval Cytoreductive Surgery for Patients With Advanced-Stage Ovarian Cancer Who Had Received Neoadjuvant Chemotherapy

Temporal and disease-site specific transcriptional and phenotypic changes in response to neoadjuvant chemotherapy in high-grade serous ovarian cancers

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