الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Clear cell renal cell carcinoma (ccRCC) incidence is increasing worldwide. About third of patients with clear cell renal cell carcinoma have metastasis at diagnosis whereas a quarter of patients with localised disease experience relapse metastasis after curative surgery. Identifying high risk patients is the most crucial challenge when reducing morbidity and mortality pertinent to ccRCC is addressed.
The present work comprised 50 cases of ccRCC. Patients’ ages ranged between 35 and 76 years , with a mean of 55. 36 ±10. 43 years and a male to female ratio of 1. 5:1.
The immunohistochemical expression ofCD8, CD163 and PD-L1 was investigated in the studied ccRCC cases. Their expression was then correlated with different clinicopathologic variables including patient´s age, sex, tumor size, microvascular invasion, necrosis in addition to tumor grade and stage.
Tumor -infiltrating lymphocytes constitute the most widely studied population of TIIC. TILs include large population of CD4+ and CD8+ T cells. CD8 expression was detected in 92% of our cases. However, this expression failed to statistically correlate with any of the studied clinicopathologic parameters including patients ´ age and gender& tumor’s nuclear grade &p T stage.
Tumor associated macrophages (TAMs), as a pivotal group of immune cells in tumor microenvironment(TME) were reported to play a critical role in tumor development. Different cytokines and chemokines activate the M1 and M2 subtypes , which constitute the two main subtypes of TAMs.
CD163,a marker of M2 TAMs, was expressed as a Histopathological score(H score). There was no statistically significant relation between either of patients’ age, gender, tumor nuclear grade , p T stage or microvascular invasion on one hand and CD163 expression on the other hand. CD163 expression showed statistically significant correlation with tumor size and presence of tumor necrosis .
The inhibitory pathways known as immune checkpoints have been widely studied in malignant tumors including RCC. Tumour cells derive advantage from activating immunosuppressive mechanisms to evade immune system attacks. The PD-1, PD-L1 pathway is the most well studied among the various checkpoint pathways. T cell inhibitory receptors are expressed on T cells and serve to inhibit the activation of cytotoxic T cells, thereby impeding their function. In the present work,PD-L1 was expressed in 10% of the studied ccRCC cases.
No significant correlation was detected between PD-L1 expression on one hand and any of patient´s age, sex, tumor size, microvascular invasion or presence of tumor necrosis. On the other hand, PD-L1 expression significantly increased in potentially aggressive tumors with high nuclear grade and advances stage.
Based on the aforementioned results , immunostaining for CD8, CD163 and PD-L1 elucidate the nature by a given tumor’s TME and hence aids in the prediction of the biological behavior of clear cell renal cell carcinoma . We were able to demonstrate that CD8+&M2 macrophages as ICs in the TME and PD-L1 can serve as prognostic and predictive biomarker for aggressive behavior of a ccRCC.