Unwrapping the immunological alterations in testicular germ cell tumors: From immune homeostasis to malignancy and emerging immunotherapies

Abstract

AbstractBackgroundTesticular germ cell tumors (TGCTs), derived from primordial germ cells, are rare malignancies with high curative potential. However, the emergence of new evidence indicating that 15% of patients experience tumor progression, leading to death, underscores the need for innovative therapeutics.ObjectivesThis review aimed to explore the immune status in maintaining testicular health and the immune‐related aspects of malignancy. Furthermore, it presents an overview of current data on the use of immunotherapy for TGCT patients.Results and DiscussionRecent advances in immunology have opened a promising avenue for studying diseases and highlighted its role in treating diseases. While the immunopathological facets of TGCTs are not fully understood, investigations suggest a complex interplay among testis‐resident immune cells, testis‐specific cells (i.e., Sertoli cells (SCs) and Leydig cells (LCs)), and immune‐regulating mediators (e.g., sex hormones) in the normal testicle that foster the testicular immune privilege (TIP). Although TIP plays a crucial role in sperm production, it also makes testis vulnerable to tumor development. In the context of cancer‐related inflammation, disruption of TIP leads to an imbalanced immune response, resulting in chronic inflammation that can contribute to testicular tissue dysfunction or loss, potentially aiding in cancer invasion and progression.ConclusionComparing the immune profiles of normal and malignant testes is valuable and may provide insights into different aspects of testicular immunity and immune‐based treatment approaches. For patients resistant to chemotherapy and with a poor prognosis, immunotherapy has shown promising results. However, its effectiveness in treating resistant TGCTs or preventing tumor recurrence is still uncertain.