Immunology of the peritoneal cavity: Relevance for host-tumor relation

Abstract

The peritoneal membrane, formed by a single layer of mesothelial cells, lines the largest cavity of the human body. Anatomic structures of the peritoneal cavity, along with resident leukocyte populations, play an important role in the defense against microorganisms invading by breaching the gut integrity or ascending through the female genital tract. Local immune mechanisms in the peritoneal cavity are also important in patients undergoing peritoneal dialysis and in women with endometriosis. There is now extensive evidence demonstrating the significance of peritoneal immune mechanisms in the control of metastatic spread. Leukocytes belonging to both the innate and adaptive immune systems are present in the peritoneal cavity of normal subjects as well as in patients with intra-abdominal cancer. There is now increased understanding of the mechanisms that not only allow the tumor cells to escape the detection and destruction by the host immune system, but also to use the inflammatory mechanisms to promote tumor growth and spread inside the peritoneal cavity. Malignant ascites represents a model for the study of the interaction between tumor cells and the host immune system as well for the analysis of the tumor microenviroment. The peritoneal immune system may be stimulated by intraperitoneal administration of biologic agents. This peritoneal immunotherapy may be used for palliation of malignant ascites, or as a consolidation strategy in patients with minimal residual disease.

IL-33 delays metastatic peritoneal cancer progression inducing an allergic microenvironment

“…39,40 This macrophage population represents the first line of defense against microbes breaching the intestine and ascendant gynecological infections. 22 As has been reported for other sites, 41-43 we observed that the peritoneal administration of IL-33 was able to promote an allergic like macrophage activation in the peritoneal tumor-associated macrophages. As reported previously for CD40 activated CD86 + activated macrophages in the microenvironment of pancreatic cancer, 44 or activated peritoneal macrophages were able to promote tumor cytotoxicity in vitro and delay tumor progression in vivo.…”

“…Therefore, the peritoneal cavity has a resident population of ontogenically differentiated resident macrophages that serve as first line of defense. 22 Allergic reactions are characterized by the presence of an activated macrophages, also described as wound-healing or M2a macrophages. 23-25 Accordingly, we found that peritoneal macrophages presented this allergic like activated phenotype shown by an increased production of Ym-1 and IL-13 (Figure 5a &b ).…”

Upstaging based solely on positive peritoneal washing does not affect outcome in endometrial cancer

“…There is now emerging evidence that a significant innate and adaptive immunity exists in the peritoneum that prevents the successful growth and propagation of tumor cells. 64 This immunity may be subverted by some tumors, allowing them to grow. The malignant potential of tumor cells within the peritoneal cavity may also be related to the number of tumor cells.…”

Tumor microenvironment and systemic disease: a dual target in medical oncology (also in the case of biomarkers)

“…Unfortunately, malignant effusions as a sample matrix are often overlooked. In addition to the identification of biomarkers that characterize the tumor cell, the analysis of malignant effusions could be useful specifically in the monitoring of the host antitumor response [22]. For example, in malignant ascites of patients with advanced malignancies the phenotype of leukocytes consistent with defective antigen presentation and costimulatory pathway have been observed [12,14].…”