Immunotherapy in Gynaecological cancers

Cancer immunotherapy is one of the most upcoming treatment strategies emerging as a fascinating option in the management of advanced gynecological cancers.

The immune system plays a key role in eliminating and controlling early tumor growth. Recognition and elimination of tumors by the immune system involves a series of steps coordinated by the various parts of the innate and adaptive immune system. Starting with the process of antigen presentation, tumors have evolved a variety of resistance mechanisms that allow for successful escape from immune recognition and elimination. Thus, immunotherapeutic approaches aim to improve recognition of tumors by the immune system and to inhibit the mechanisms of immune escape.

With recent data demonstrating promising activity in various tumor types, many of these approaches have been explored in gynecologic malignancies as well. During the last years, significant progress in the understanding of signaling pathways of immune cells has revived the field of immunotherapy for cancer. Emerging data demonstrate that tumorigenesis resulting in ovarian, uterine, and cervical cancers is a consequence of impaired host immune responses to cancerous cells.

Leveraging the immune system through the use of immune checkpoint inhibitors, therapeutic vaccine therapy, and adoptive cell transfer presents a profound opportunity to revolutionize cancer treatment. The development of immune-based antitumor approaches has led to safer treatment options that give fruitful results in these malignancies.

Cancers that start in a woman’s reproductive system are called gynaecological cancers. It refers to the following five cancers that start in a woman’s reproductive system. Immunotherapeutic advancements in these cancers are:

• Ovarian cancer:

Studies in epithelial ovarian carcinoma suggest that it is an excellent candidate for immunotherapeutic approaches. Initial results of several of the combining strategies of immunotherapy, PARP inhibitor, and antiangiogenic therapy show promising results.

• Womb cancer (also known as endometrial or uterine cancer):

Several studies have now confirmed the clinical utility of Immune checkpoint inhibitors as a monotherapy in endometrial cancers. Studies investigating two immunotherapeutic agents, and immunotherapy with other targeted agents are also being explored for endometrial malignancies.

• Cervical cancer :

In cervical cancers, studies suggest that PD-L1 and PD-1 expression correlate with tumor progression and tumor metastasis, responses to monotherapy ICI have shown only modest responses.

• Vaginal cancer :

Various Immunotherapeutic agents along with radiation therapy are currently being tested for vaginal tumors (NCT03452332, NCT03277482).

• Vulvar cancer:

 The phase I/II CheckMate 358 trial found that nivolumab showed activity in a cohort of patients with recurrent or metastatic cervical, vaginal, and vulvar squamous cell carcinoma. 

Immunotherapy, mainly in the form of immune checkpoint inhibitors, has been transformative in gynecological cancers. The approved immune checkpoint inhibitors, the so-called “first generation,” include monoclonal antibodies directed against PD-1 (pembrolizumab, nivolumab, cemiplimab) against PD-L1 (atezolizumab, avelumab, and durvalumab) and against protein CTLA-4 (ipilimumab). Immune checkpoint inhibitors have gained considerable attention because of their impressive treatment outcomes in a wide range of tumor types, including those once considered difficult-to-treat cancers.  Gynecological cancers are relatively well tolerated as single agents, particularly when compared with cytotoxic chemotherapy. Immunotherapy has heralded a new era for cancer treatment, which we hope extends to women with gynecologic cancers.

By- Fatma

Sources

https://www.cancerresearchuk.org/about-cancer/womens-cancer

https://www.rcog.org.uk/en/patients/menopause/gynaecological-cancers/

https://ascopubs.org/doi/full/10.1200/EDBK_237967