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

BACKGROUND: Testicular 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. OBJECTIVES: This 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 DISCUSSION: Recent 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. CONCLUSION: Comparing 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.

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.

BACKGROUND: Seminoma and dysgerminoma are rare testicular and ovarian germ cell tumors characterized by a significant infiltration of immune cells in the tumor microenvironment. According to the failure of conventional treatments in some patients, it is crucial to identify novel prognostic and therapeutic biomarkers for these patients. The objectives of this study were to evaluate the expression of CD45RO and PD-1/PD-L1 and investigate their association with the clinicopathological characteristics of the patients. METHODS: Immunohistochemistry was performed to assess the expression of CD45RO, PD-1, and PD-L1 in tumor-infiltrated lymphocytes (TILs), and tumor cells in 33 seminoma and 31 dysgerminoma patients. The expression levels were evaluated using a semiquantitative approach, weighted histoscore, which considers both the intensity and extent of staining. RESULTS: All seminoma and dysgerminoma patients exhibited CD45RO expression in TILs, with 66.7 % and 90.3 % displaying high levels of expression, respectively. PD-1 expression in TILs was observed at low levels in 81.8 % and 77.4 % and at high levels in 18.2 % and 19.4 % of seminoma and dysgerminoma patients, respectively. Likewise, low expression of PD-L1 in tumor cells was detected in 63.6 % of seminoma and 61.3 % of dysgerminoma patients, while none of the patients exhibited high expression of PD-L1. In seminoma patients, a positive correlation was observed between PD-1 expression in TILs and CD45RO expression and between PD-L1 expression in tumor cells and TILs score. CONCLUSION: The frequent infiltration of CD45RO, along with variable expression of PD-1 and PD-L1 on TILs and tumor cells, could impact the effectiveness of anti-tumor responses and immunotherapy.

Leishmania tropica: suggestive evidences for the effect of infectious dose on pathogenicity and immunogenicity in an experimental model.

Leishmania (L.) tropica is a causative agent of cutaneous and occasionally visceral or viscerotropic leishmaniasis in humans. The dose of parasites influences the course and outcome of disease in some Leishmania species. The effect of parasite dose on L. tropica infection in an experimental model was studied in the current paper. High and low doses of L. tropica were used for ear infection of BALB/c mice and lesion development, parasite load, and cytokine responses were assessed. L. major infection was used for comparison. Pre-infected mice were challenged in the footpad by a fixed high dose of L. tropica, and immune response and protection level were evaluated. High dose L. tropica infection in comparison to low dose results in higher lesion diameters, higher load of parasite in draining lymph node, higher levels of interferon-γ and interleukin-10, dissemination of parasite to spleen, and induction of protection against further L. tropica challenge. Comparison of L. tropica with L. major showed that L. tropica results in lower lesion diameters, more potential for growth in lymph nodes at early phases of infection, parasite dissemination to spleen, lower levels of IL-10, and a permanent lower cytokine response against low parasite dose in comparison to high dose. Our findings suggest that for L. tropica infection, only the high dose results in visceralization of the parasite and protection against further challenge of L. tropica. Therefore, the parasite dose may be an important factor in pathogenesis and immunity in L. tropica infection.