Abstract
Introduction: Women with epithelial ovary cancer with impaired immunity develop life-threatening clinical disease, implying that these patients have some form of altered immune response against disease prognosis. Frequent findings of tumor-associated lymphocytes as well as differential immunologic markers from tumor specimen after surgery for EOC are explicit evidence of immunologic sensitivity to this. Despite several treatment modalities, the majority of these patients will eventually relapse. However, several i.p. therapies have been advocated to command the disease progress. In this context, hyperthermia is one of the effective i.p. therapies to boost the therapeutic efficacy, showing its impact by killing tumor cells as well as inducing an efficient anticancer immune response, therefore providing insight into hyperthermic intraperitoneal chemotherapy (HIPEC)-associated immunotherapy, a new therapeutic treatment for cancer.
Rationale: In a vast majority of the cases the disease is confined to the peritoneal cavity for a long time. Even in recurrent cases, disease remains confined to peritoneal cavity only. Intraperitoneal administration of chemotherapy results in high peritoneal to plasma ratios for pick concentration of chemotherapeutic drugs. Mechanisms of immune activation: Surface molecular expression—Heated tumor cells increase the surface expression of MHC class I, making the tumor cells more sensitive to lysis by CD8+T (T cytotoxic) cells. Expression of HSPs—Heated tumor cells release heat shock protein (HSPs), which activate natural killer (NK) cells and antigen-presenting cells (APCs), cross present the antigen to CD8+T cells. Exosome production—Heated tumor cells release exosomes, containing potential antigens, and antigen-presenting cells, cross present the antigen to CD8+ T cells. Direct effect on immune cells, NK cells, CD8+ T cells and dendritic cells (DC), tumor vasculature—Increases the permeability of tumor vasculature. Changed vasculature within the tumor may help immune cell mobilization.
Conclusion: HIPEC elicits antitumor immune responses by enabling tumor cells to stimulate the immune system through increased surface expression of MHC class I, release of HSPs, exosomes, directly activating intratumoral immune cells and improving immune-cell trafficking.
Note: This abstract was not presented at the conference.
Citation Format: Arshi Rizwan, Mukurdipi Ray. Effect of HIPEC on immune microenvironment in epithelial ovary cancer [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr B79.
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