Cure Alveolar Soft Part Sarcoma International (iCureASPS)

Abstract

Many proliferative, invasive, and immune tolerance mechanisms that support normal human pregnancy are also exploited by malignancies to establish a nutrient supply and evade or edit the host immune response. In addition to the shared capacity for invading through normal tissues, both cancer cells and cells of the developing placenta create a microenvironment supportive of both immunologic privilege and angiogenesis. Systemic alterations in immunity are also detectable, particularly with respect to a helper T cell type 2 polarization evident in advanced cancers and midtrimester pregnancy. This review summarizes the similarities between growth and immune privilege in cancer and pregnancy and identifies areas for further investigation. Our PubMed search strategy included combinations of terms such as immune tolerance, pregnancy, cancer, cytokines, angiogenesis, and invasion. We did not place any restrictions on publication dates. The knowledge gained from analyzing similarities and differences between the physiologic state of pregnancy and the pathologic state of cancer could lead to identification of new potential targets for cancer therapeutic agents.

CTL = CD8+ T cytotoxic lymphocyte; DC = dendritic cell; EVT = extravillous trophoblast; HLA = human leukocyte antigen; IL = interleukin; NK = natural killer; TH1 = helper T cell type 1; TH2 = helper T cell type 2; Treg = regulatory T cell; uNK = uterine NK

Immune privilege is thought to reflect an evolutionary adaptation to protect vital structures from damage by inflammatory responses directed against pathogens. It was originally believed that antigens in immune-privileged sites are concealed from the immune system by physical barriers and therefore ignored.

https://www.ncbi.nlm.nih.gov ›

Even unexpected tissues, such as the gut,36 tumors,37 skin, and lymph node itself have been included as immune-privileged sites under certain circumstances

Immune privilege or privileged immunity?

https://www.nature.com/articles/mi200827

Re: Cancer and Pregnancy: Parallels in Growth..

A substantial body of literature exists describing the mechanisms cancer cells use to escape apoptosis and migrate through normal structures while evading a host immune response. What is not well known, however, is how these complex and interrelated mechanisms are orchestrated, starting with modulation of the immune response within the tumor microenvironment and ending with migration and proliferation of cancer cells at distant sites. One potential model to further study how a single malignant cell could proliferate and then metastasize undetected within a host is that of normal human pregnancy, in which the developing placenta invades the uterus and a semiallogeneic fetus escapes rejection from the maternal immune system.1 A multitude of immunomodulatory properties of the fetomaternal interface (placenta) have evolved to allow the survival of the immunologically distinct fetus to parturition without an attack from the maternal immune system. The similarities between the mechanisms involved in fetomaternal and tumor-associated immunologic tolerance are intriguing and suggest a common pattern; however, neither system of immune evasion is perfect. A clear example of placental failure to protect the fetus against maternal immunity is that of Rh incompatibility. In multiparous women sensitized against fetal Rh antigens, re-exposure to fetal Rh antigens with subsequent pregnancy may lead to hemolytic disease of the newborn and fetal death.2 Such imperfections of shared mechanisms of immune tolerance between pregnancy and cancer suggest that cancer rejection via immunologic means may be possible, even considering the myriad mechanisms extending immunologic privilege to the fetus as well as cancer cells.

This review summarizes the parallels in proliferation, invasion, and immune privilege between cancer and pregnancy by first detailing shared characteristics of fetal-derived trophoblast cells of the placenta and tumor cells. It then describes the similarities between tolerogenic systems within the tumor microenvironment and the fetomaternal interface. Finally, it provides an overview of the evidence for systemic immune modulation in cancer and pregnancy and suggests the implications of these similarities in designing an integrated approach to cancer therapy. Our PubMed search strategy included combinations of terms such as immune tolerance, pregnancy, cancer, cytokines, angiogenesis, and invasion. We also searched for articles on cellular subsets, including natural killer (NK) cells, dendritic cells (DCs), regulatory T cells (Treg), and other lymphocyte populations with respect to their presence and function in pregnancy and cancer. We did not place any restrictions on publication dates. A better understanding of how the maternal immune system is altered during the normal processes of implantation, gestation, and labor may translate into individualized, novel therapies aimed at restoring immune competency in patients with advanced malignancies.

SHARED CHARACTERISTICS OF TROPHOBLAST CELLS AND TUMOR CELLS
Five days after fertilization, the human zygote forms into a structure consisting of 2 primary cell lines: the inner cell mass (or embryoblast) and the trophoblast.3 Trophoblast cells constitute the outer layer of the blastocyst, rapidly proliferating and invading the maternal endometrial decidua around day 7. A monolayer of cytotrophoblast cells surrounds the embryonic disc as the embryo completely embeds beneath the uterine decidua. By day 9, cytotrophoblast cells have differentiated into 2 distinct cell types: the syncytiotrophoblast and the extravillous trophoblast (EVT). The multinucleated syncytiotrophoblast cells form the external layer and are terminally differentiated. These cells are involved in fetomaternal nutrient exchanges and endocrine functions (such as β-human chorionic gonadotropic production). In contrast, EVT cells have a proliferative and invasive phenotype, migrating through the syncytiotrophoblast into the uterine wall to anchor the placenta beginning around day 14 after implantation.4 These EVT cells display a phenotype strikingly similar to cancer cells with their capacity for proliferation, migration, and establishment of a blood supply, making them a compelling model for oncologic comparison (Figure). This review highlights several shared characteristics of trophoblast and tumor cells and discusses them in the context of existing or developmental targeted cancer therapeutics (Table 1).

Perhaps this area of research is more relevant to ASPS than to many other cancers as we have seen progression of our pregnant patients in their third part of the term. Not once but few times.

Hello Olga,

It’s an interesting observation that the 3rd trimester is what you’ve noticed some of the ASPS patience developing growth, progression.


“Abstract

Maternal metabolism changes substantially during pregnancy. Early gestation can be viewed as an anabolic state in the mother with an increase in maternal fat stores and small increases in insulin sensitivity. Hence, nutrients are stored in early pregnancy to meet the feto-placental and maternal demands of late gestation and lactation. In contrast, late pregnancy is better characterized as a catabolic state with decreased insulin sensitivity (increased insulin )resistance. An increase in insulin resistance results in increases in maternal glucose and free fatty acid concentrations, allowing for greater substrate availability for fetal growth.


https://pubmed.ncbi.nlm.nih.gov/17982337/

* Hyperinsulinemia

Angiopoietin-2 (ANG-2) mediates endothelial inflammation to initiate atherosclerosis and angiogenesis. Here we determined the serum levels of ANG-2 in hyperinsulinemic subjects and whether insulin increases its expression and release.

There are a myriad of changes /possible complications taking place throughout a womens pregnancy , and a couple of the issues that come to mind are hypertension and or hypercalcemia, which both can contribute to sarcoma progression.

Tumor-induced hypercalcemia (TIH) is a frequent complication of advanced cancer, but it has been rarely reported in patients with sarcoma. We describe the case of a young female patient with TIH and with an extensive synoviosarcoma of the left lower limb destroying the bony structures.

https://pubmed.ncbi.nlm.nih.gov/8888806/

Also hormone driven cancers ,that have been found to of produced cancers during pregnancies ,are reported as followed :


“The most common gestational cancers are those appearing during the reproductive period of a woman. Breast cancer and cervical cancers are the most frequently diagnosed malignancies followed by hematological tumors and melanoma”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4921935/