Abstract
Epithelial ovarian cancer (EOC) is the leading cause of death among gynecological malignancies. Despite surgery and chemotherapy, 5-years survival rates have improved only modestly over the past few decades remaining at 45% for advanced stages. Therefore, novel therapies are urgently needed. The presence of tumor-infiltrating lymphocytes (TILs) in OC tumor microenvironment (TME) has already proved to be correlated with overall survival (OS), while immune evasion mechanisms are associated with poor prognosis. Although these data indicate that immunotherapy has a strong rationale in OC, single agent immune-checkpoints inhibitors (ICIs) have shown only modest results in this malignancy. In this review, we will discuss immune-targeting combination therapies and adoptive cell therapy (ACT), highlighting the challenges represented by these strategies, which aim at disrupting the stroma-tumor barrier to boost immune system against ovarian cancer.
Highlights
Epithelial ovarian cancer (EOC) is the leading cause of death among women with gynecological malignancies with 22,530 estimated new cases and 13,980 deaths in 2019 in the USA [1]
We focus on the strategies and challenges represented by immune-targeting combinaticoonmsbiinnattihoensminotshteamdovstaandcveadncsetdasgtaegseos fofddeevveellooppmmenetnint EinOCE.OWCe.aWlsoedaelsscoribdeecshcarlliebnegecshaanldlenges and advances aidnvaandcoespitnivaedocpetlivl ethceelrl athpeyrap(Ay C(ATC)T)wwhhiicch, ddeespsipteittehethliemiltiemd idtaetda advaaitlaabalevianilEaObClesoinfaEr,OC so far, represent areuprneisqenuteaoupnpiqouretoupnpiotyrtutnoiteyntho aennhcaenicme immmununee-r-reessppoonnssee“h“ehaetiantginthgetfhiree”fiargea”inastgOaiCn(sFtigOuCre (Figure 1)
New and more effective treatment modalities of immunotherapy are being investigated in EOC based on tumor biology, its relationship with tumor microenvironment (TME) and the immune-suppressive networks that make this cancer difficult to tackle with single agent immune checkpoints-inhibitors (ICIs)
Summary
Epithelial ovarian cancer (EOC) is the leading cause of death among women with gynecological malignancies with 22,530 estimated new cases and 13,980 deaths in 2019 in the USA [1]. Patients with T-cell-rich tumors experience longer progression-free and overall survival [10], while immune evasion mechanisms are associated with poor survival [11,12,13,14,15]. All these evidences taken together suggest that EOC patients could potentially benefit from immunotherapy. The first ones are characterized by the presence in On ththeectounmtorrabryed, coofladhtiughmdoernssiatyreofcChDar8a+ cTtecerlilzse[d23,b24y],thwehoasbe sfeunnccteionoafliTty ccealnlsbeinimtupamireodr bbyeds and at immunosuppressive networks Such patients could benefit from therapies acting on T cell checkpoint tumor edginevsoalvnedd ianriemgmeunneer-taollleyraanffcee.cted by a failure in T cell priming reflecting the need of strategies that could deliOvnerthaeucotonltroagryo,ucso/ladltluomgeornsicareffcheacrtaocrtecriezlelds ibnyttohethaebsceancnecoefr.T cells in tumor beds and at. ACT (a): Tumor-infiltrating lymphocites (TILs) are isolated from surgically resected tumor samples, expanded in vitro and reinfused into the lymphodepleted patient; (b): T cells from patient peripheral blood are isolated and expanded in culture and genetically modified to express either a T cell receptor (TCR) or a chimeric antigen receptor (CAR) that confers the ability to recognize and destroy tumor-cells when re-infused into the the lymphodepleted patient
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