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Serial Immune Profiling During Intraperitoneal Chemotherapy Shows Changes in Loco-regional Immunity in Ovarian Cancer

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE217179 | GEO | 2023/06/02

REPOSITORIES: GEO

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Serial Immune Profiling During Intraperitoneal Chemotherapy Shows Changes in Loco-regional Immunity in Ovarian Cancer [III]

Project description:The immune system is active in the tumor microenvironment (TME) of epithelial ovarian cancer (EOC) and carries both effector and suppressive functions. We profiled biomarker expression on serial biological specimens collected during intraperitoneal (IP) chemotherapy to better define treatment-induced tumor involution.

2023-06-02 | GSE217178 | GEO

Serial Immune Profiling During Intraperitoneal Chemotherapy Shows Changes in Loco-regional Immunity in Ovarian Cancer [I]

2023-06-02 | GSE217175 | GEO

Serial Immune Profiling During Intraperitoneal Chemotherapy Shows Changes in Loco-regional Immunity in Ovarian Cancer [II]

2023-06-02 | GSE217177 | GEO

Serial Immune Profiling During Intraperitoneal Chemotherapy Shows Changes in Loco-regional Immunity in Ovarian Cancer

Project description:Serial Immune Profiling During Intraperitoneal Chemotherapy Shows Changes in Loco-regional Immunity in Ovarian Cancer

| PRJNA897854 | ENA

Serial Immune Profiling During Intraperitoneal Chemotherapy Shows Changes in Loco-regional Immunity in Ovarian Cancer [I]

Project description:Serial Immune Profiling During Intraperitoneal Chemotherapy Shows Changes in Loco-regional Immunity in Ovarian Cancer [I]

| PRJNA897856 | ENA

Serial Immune Profiling During Intraperitoneal Chemotherapy Shows Changes in Loco-regional Immunity in Ovarian Cancer [II]

Project description:Serial Immune Profiling During Intraperitoneal Chemotherapy Shows Changes in Loco-regional Immunity in Ovarian Cancer [II]

| PRJNA897858 | ENA

Serial Immune Profiling During Intraperitoneal Chemotherapy Shows Changes in Loco-regional Immunity in Ovarian Cancer [III]

Project description:Serial Immune Profiling During Intraperitoneal Chemotherapy Shows Changes in Loco-regional Immunity in Ovarian Cancer [III]

| PRJNA897859 | ENA

Phase I Trial Combining Chemokine-Targeting with Loco-Regional Chemoimmunotherapy for Recurrent, Platinum-Sensitive Ovarian Cancer Shows Induction of CXCR3 Ligands and Markers of Type 1 Immunity.

Project description:PurposeIncreased prevalence of cytotoxic T lymphocytes (CTL) in the tumor microenvironment (TME) predicts positive outcomes in patients with epithelial ovarian cancer (EOC), whereas the regulatory T cells (Treg) predict poor outcomes. Guided by the synergistic activity of TLR3 ligands, IFNα, and COX-2 blockers in selectively enhancing CTL-attractants but suppressing Treg-attractants, we tested a novel intraperitoneal chemoimmunotherapy combination (CITC), to assess its tolerability and TME-modulatory impact in patients with recurrent EOC.Patients and methodsTwelve patients were enrolled in phase I portion of the trial NCT02432378, and treated with intraperitoneal cisplatin, intraperitoneal rintatolimod (dsRNA, TLR3 ligand), and oral celecoxib (COX-2 blocker). Patients in cohorts 2, 3, and 4 also received intraperitoneal IFNα at 2, 6, and 18 million units (MU), respectively. Primary objectives were to evaluate safety, identify phase 2 recommended dose (P2RD), and characterize changes in the immune TME. Peritoneal resident cells and intraperitoneal wash fluid were profiled via NanoString and Meso Scale Discovery (MSD) multiplex assay, respectively.ResultsThe P2RD of IFNα was 6 MU. Median progression-free survival and overall survival were 8.4 and 30 months, respectively. Longitudinal sampling of the peritoneal cavity via intraperitoneal washes demonstrated local upregulation of IFN-stimulated genes (ISG), including CTL-attracting chemokines (CXCL-9, -10, -11), MHC I/II, perforin, and granzymes. These changes were present 2 days after chemokine modulation and subsided within 1 week.ConclusionsThe chemokine-modulating intraperitoneal-CITC is safe, tolerable, and associated with ISG changes that favor CTL chemoattraction and function. This combination (plus DC vaccine) will be tested in a phase II trial. See related commentary by Aranda et al., p. 1993.

| S-EPMC9106847 | biostudies-literature

Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer.

Project description:Hyperthermic intraperitoneal chemotherapy (HIPEC) in conjunction with cytoreductive surgery (CRS) holds promise as an adjunctive treatment strategy in malignancies affecting the peritoneal surface, effectively targeting remaining microscopic residual tumor. HIPEC increases concentrations of chemotherapy directly within the peritoneal cavity compared with the intravenous route and reduces the systemic side effects associated with prolonged adjuvant intraperitoneal exposure. Furthermore, hyperthermia increases tissue penetration and is synergistic with the therapeutic chemotherapy agents used. In ovarian cancer, evidence is building for its use in both primary and recurrent scenarios. In this review, we examine the history of HIPEC, the techniques used, and the available data guiding its use in primary and recurrent ovarian cancer.

| S-EPMC7168334 | biostudies-literature

Hyperthermic Intraperitoneal Chemotherapy-Induced Molecular Changes in Humans Validate Preclinical Data in Ovarian Cancer.

Project description:PurposeHyperthermic intraperitoneal chemotherapy (HIPEC) confers a survival benefit in epithelial ovarian cancer (EOC) and in preclinical models. However, the molecular changes induced by HIPEC have not been corroborated in humans.Patients and methodsA feasibility trial evaluated clinical and safety outcomes of HIPEC with cisplatin during optimal cytoreductive surgery (CRS) in patients with EOC diagnosed with stage III, IV, or recurrent EOC. Pre- and post-HIPEC biopsies were comprehensively profiled with genomic and transcriptomic sequencing to identify mutational and RNAseq signatures correlating with response; the tumor microenvironment was profiled to identify potential immune biomarkers; and transcriptional signatures of tumors and normal samples before and after HIPEC were compared to investigate HIPEC-induced acute transcriptional changes.ResultsThirty-five patients had HIPEC at the time of optimal CRS; all patients had optimal CRS. The median progression-free survival (PFS) was 24.7 months for primary patients and 22.4 for recurrent patients. There were no grade 4 or 5 adverse events. Anemia was the most common grade 3 adverse event (43%). Hierarchical cluster analyses identified distinct transcriptomic signatures of good versus poor responders to HIPEC correlating with a PFS of 29.9 versus 7.3 months, respectively. Among good responders, significant HIPEC-induced molecular changes included immune pathway upregulation and DNA repair pathway downregulation. Within cancer islands, % programmed cell death protein 1 expression in CD8+ T cells significantly increased after HIPEC. An exceptional responder (PFS 58 months) demonstrated the highest programmed cell death protein 1 increase. Heat shock proteins comprised the top differentially upregulated genes in HIPEC-treated tumors.ConclusionDistinct transcriptomic signatures identify responders to HIPEC, and preclinical model findings are confirmed for the first time in a human cohort.

| S-EPMC8984280 | biostudies-literature

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