Efficacy evaluation of multi-immunotherapy in ovarian cancer: From bench to bed

Abstract

Ovarian cancer, one of the most common gynecological malignancies, is characterized by high mortality and poor prognosis. Cytoreductive surgery and chemotherapy remain the mainstay of ovarian cancer treatment, and most women experience recurrence after standard care therapies. There is compelling evidence that ovarian cancer is an immunogenic tumor. For example, the accumulation of tumor-infiltrating lymphocytes is associated with increased survival, while increases in immunosuppressive regulatory T cells are correlated with poor clinical outcomes. Therefore, immunotherapies targeting components of the tumor microenvironment have been gradually integrated into the existing treatment options, including immune checkpoint blockade, adoptive cell therapy, and cancer vaccines. Immunotherapies have changed guidelines for maintenance treatment and established a new paradigm in ovarian cancer treatment. Despite single immunotherapies targeting DNA repair mechanisms, immune checkpoints, and angiogenesis bringing inspiring efficacy, only a subset of patients can benefit much from it. Thus, the multi-immunotherapy investigation remains an active area for ovarian cancer treatment. The current review provides an overview of various clinically oriented forms of multi-immunotherapy and explores potentially effective combinational therapies for ovarian cancer.

Immune pathway through endometriosis to ovarian cancer

“…ACT has brought about a significant breakthrough in treating blood-related tumors. However, when it comes to solid tumors like ovarian cancer, ACT appears to be inadequate in inducing substantial anti-tumor responses[ 255 ]. Up until now, there has not been a notable therapeutic effectiveness.…”

“…Vaccination plays a crucial role in immunotherapy, offering advantages to individuals affected by diverse forms of cancer, and there is extensive research into therapeutic vaccines in the context of ovarian cancer. The investigation into the potential of single application of a cancer vaccine for ovarian cancer is ongoing, and this includes the examination of various types of vaccines such as peptide vaccines, whole tumor cell vaccines, cancer stem cell vaccines, APC vaccines, DNA/RNA vaccines, bacterial vaccines, and more[ 255 ]. Many of these vaccines enhance the body's immune response against ovarian cancer, but clinical evidence has only demonstrated modest effectiveness in the majority of patients[ 257 - 259 ].…”

Immune modulation of innate and adaptive responses restores immune surveillance and establishes anti-tumor immunological memory

“…In situ vaccination (ISV) has been proposed as an efficient approach to remodel the tumor from "cold" to "hot" while boosting anti-tumor T cell response (17). However, the selection of the most efficient antigen, which represents the heterogeneity of the tumor has proven to be a major challenge (18)(19)(20). A promising strategy is to develop personalized vaccination by inducing cancer cell death and enhancing antigen presentation.…”

The role of pyroptosis-related lncRNA risk signature in ovarian cancer prognosis and immune system

“…Immunotherapy could stimulate peripheral immune response, enhance local and systemic immunity. For instance, targeting PD-1 (nivolumab, pembrolizumab), CTLA-4 (tremelimumab, ipilimumab) and PD-L1 (avelumab, durvalumab, aterolizumab) has been reported to treat ovarian cancer patients [ 7 – 9 ]. Programmed cell death (PCD) includes apoptosis, autophagy, necroptosis, pyroptosis, ferroptosis and cuproptosis [ 10 , 11 ].…”