Frequent expression of CD45RO memory T cell marker as well as low to high expression of PD-1 and PD-L1 inhibitory molecules in seminoma and dysgerminoma

Germ cell tumors are diverse and uncommon malignancies originating from germ cells in gonads or extragonadal sites. The gonads, including ovaries and testicles, are the most common sites for developing these tumors (Abughanimeh and Teply, 2021). Testicular germ cell tumors (TGCTs) account for only 1 % of all cancers in men but are the most frequent testicular malignancies. TGCTs are heterogeneous and can be classified into seminomas and non-seminomas. Seminoma is responsible for approximately half of all TGCTs (Cedeno et al., 2022, Lamichhane and Mukkamalla, 2023). The ovarian counterpart of testicular seminoma is known as dysgerminoma (Tsutsumi et al., 2020). Dysgerminoma is an ovarian malignant germ cell tumor (OMGCT) that mainly occurs in young women. It represents approximately 1 % to 5 % of all ovarian cancers and 45 % of OMGCTs (Kaur, 2020). Both dysgerminoma and seminoma are often associated with a favorable prognosis and a good overall survival rate (>95 %) (Banna et al., 2019, Kilic et al., 2021). Surgical procedures are the primary treatment for these tumors and chemotherapy or radiotherapy may be recommended for advanced cases (Arndt et al., 2022, Hellesnes et al., 2020). However, some cases do not respond to conventional therapies, experience recurrence, and may suffer short- or long-term side effects after chemotherapy or radiotherapy (Sadigh et al., 2020). It is also worth mentioning that since these diseases affect patients at a sensitive stage of life, during their youth and fertility, they can have irreversible effects on their lives (Giona, 2022, Coleman et al., 2022). Therefore, discovering diagnostic and prognostic markers and developing new treatment strategies with higher efficacy and lower toxicity levels are crucial (Harahap et al., 2020). Many studies have highlighted the association between immune responses and cancer biology (review in Costa et al., 2021). T lymphocytes are the most abundant and well-described immune cells in the tumor microenvironment (TME) (Fridman et al., 2012, Fridman et al., 2017). CD45RO+ tumor-infiltrating lymphocytes (TILs) are memory cells (Kwiecień et al., 2022). CD45RO+ T cells have been shown to have anti-tumor functions, and their favorable prognostic value has been demonstrated in various human cancers (Hu and Wang, 2017, Huang et al., 2019, Zhou et al., 2019, Koike et al., 2021, Ahmadvand et al., 2019, Wang et al., 2015). The rapid advancements in immunotherapy have been driven by our growing understanding of the role of tumor microenvironment in cancer progression. One effective strategy involves targeting inhibitory checkpoint molecules (Drakes et al., 2018, Vaddepally et al., 2020). One of the prominent checkpoint inhibitor pathways is the programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway. PD-1 plays a pivotal role in regulating the balance between T-cell activation, immune tolerance, and potential tissue damage caused by immune-mediated responses by engaging with its ligands, PD-L1 and PD-L2 (Ai et al., 2020, Kornepati et al., 2022). There is strong evidence that the expression levels of these molecules increase in different types of cancers (Munari and Mariotti, 2021, Gerdabi et al., 2023). Within the TME, the interaction between PD-1 expressed in T cells and PD-L1 expressed in tumor cells contributes to the suppression of the immune response against the tumor. This interaction ultimately enables the tumor cells to evade the effective immune responses and contribute to the tumor progression (Doroshow et al., 2021, Han et al., 2020). So far, a number of studies have investigated the expression of PD-1 and PD-L1 in seminoma and dysgerminoma patients. These studies indicated that PD-1 and PD-L1 can be expressed at different levels in these patients (Boldrini et al., 2019, Chovanec et al., 2017, Cierna et al., 2016, Fankhauser et al., 2015a, Harahap et al., 2020, Lu et al., 2019, Sadigh et al., 2020). Patients with advanced cancers have been shown to benefit from anti-PD-1 or anti-PD-L1 agents (Guo et al., 2020). To the best of our knowledge, there has been no study investigating the expression of CD45RO, PD-1, and PD-L1 in seminoma and dysgerminoma simultaneously. Therefore, the current study was conducted to investigate the expression of CD45RO, which serves as an indicator for the presence of memory T cells and PD-1/PD-L1 as common immune checkpoint molecules in TILs and tumor cells and their correlation with clinicopathological characteristics of seminoma and dysgerminoma patients.

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