Leveraging immunotherapy for the treatment of gynecologic cancers in the era of precision medicine

Abstract

During the past decade significant progress in the understanding of stimulatory and inhibitory signaling pathways in immune cells has reinvigorated the field of immuno-oncology. In this review we outline the current immunotherapy based approaches for the treatment of gynecological cancers, and focus on the emerging clinical data on immune checkpoint inhibitors, adoptive cell therapies, and vaccines. It is anticipated that in the coming years biomarker-guided clinical trials, will provide for a better understanding of the mechanisms of response and resistance to immunotherapy, and guide combination treatment strategies that will extend the benefit from immunotherapy to patients with gynecologic cancers.

The role of the vaginal microbiome in gynaecological cancer

“…In another study, the presence of Bacteroides thetaiotaomicron or Bacteroides fragilis was necessary for the success of immunotherapy targeting CTLA‐4 in both humans and mice . This type of immunotherapy is also under investigation as a treatment for gynaecological cancers, and the vaginal microbiome could similarly influence its effectiveness. Probiotics alone have been shown to be sufficient to prevent sarcomas in mice by reducing the level of gut Th17 inflammation and promoting anti‐inflammatory Treg cells .…”

A Leishmania murine model to evaluate the immunomodulatory properties of Pythium insidiosum proteins

“…A recent review on the use of immunotherapy to treat infectious and non-infectious diseases highlights the fascinating capabilities that some microbial proteins possess to modulate the immune response [34, 35, 36]. However, few immunotherapeutic proteins of microbial origin are presently being considered for immunotherapy; one of them is PiV, while the rest represent antigenic epitopes harvested from cancer patients [33, 37].…”

Early disease progression and treatment discontinuation in patients with advanced ovarian cancer receiving immune checkpoint blockade

“…Based on these findings, therapy with immune checkpoint blockade (ICB) has been evaluated in several trials in epithelial ovarian cancer (EOC). However, compared to some solid tumors, the response rates of EOC patients have been modest [2][3][4]. Furthermore, the median progression-free survival reported in all EOC studies is very short, typically coinciding with the first protocol-defined scan, leading to treatment discontinuation in the majority of patients [2][3][4].…”

“…However, compared to some solid tumors, the response rates of EOC patients have been modest [2][3][4]. Furthermore, the median progression-free survival reported in all EOC studies is very short, typically coinciding with the first protocol-defined scan, leading to treatment discontinuation in the majority of patients [2][3][4]. While an effort is ongoing to identify the patients that are more likely to derive benefit from ICB, it is equally important to determine which patients are the ones that are more likely to discontinue before the first scan and thus are unlikely to derive benefit.…”