The Association of Tumor Immune Microenvironment of the Primary Lesion with Time to Metastasis in Patients with Renal Cell Carcinoma: A Retrospective Analysis

Abstract

Biological or immunological differences in primary lesions between synchronous and metachronous metastatic renal cell carcinoma (mRCC) have been reported. However, the association between the tumor immune microenvironment (TIME) of primary lesions and time to metastasis remains unknown. We investigated the differences in the TIME of primary lesions based on time intervals to metastasis, mainly between the synchronous group (SG; metastasis within 3 months) and metachronous group (MG; metastasis after 3 months), and its association with clinicopathological parameters in patients with mRCC. Overall, 568 patients treated first-line with vascular endothelial growth factor receptor inhibitors comprised the analysis population (SG: N = 307 [54.0%]; MG: N = 261 [46.0%]). SG had a higher proportion of patients with poor prognostic pathological feature tumors: WHO/ISUP grade 4, necrosis, lymphovascular invasion, infiltrative growth pattern, and sarcomatoid differentiation. Regarding the TIME, more immunogenic features were seen in SG than MG, with a higher PD-L1 positivity and a lower proportion of the desert phenotype. This is the first study to examine the differences in the TIME of primary lesions in patients with mRCC based on the time intervals to metastasis. The TIME of primary lesions could affect the time to metastasis.

Tumor microenvironment and clinical efficacy of first line immunotherapy-based combinations in metastatic renal cell carcinoma

“…In our experience, we provide a pathological characterization of TME of tumor blocks from patients treated with first line ICI-based treatment using multiple IHC assay. In case of metachronous presentation, only cases with histological material from no more than 3 months before the diagnosis of metastatic stage were included, in order to minimize any discrepancies in the representation of TME of metastatic disease as much as possible [ 17 ].…”

The Cellular Stress and Cutaneous Manifestations in Renal Cell Carcinomas—A Narrative Review

“…The skin often signals systemic changes. Secondary cutaneous events may occur concurrently with RCC, disappear after tumor removal, and increase with tumor recurrence or metastatic disease [5,[47][48][49]. The skin can be directly or indirectly involved in malignant kidney conditions [5].…”

Clear Cell Renal Cell Carcinoma: A Test Bench for Investigating Tumor Complexity

“…Here, basic researchers and clinicians from Italy, Japan, USA, Spain, South Africa, Sweden, Romania, and Germany present their findings from very different perspectives, i.e., the role of the complement system in the immune background of tumors [4], imagingbased biomarker identification [5], the relevance of the immune microenvironment [6,7], the influence of clock genes and the circadian rhythm in tumor therapy [8], the morphological/molecular characteristics of cystic CCRCCs [9], the single-cell RNA-sequencing signature of primary and metastatic neoplasms [10], an extensive review of tumor biomarkers in CCRCC [11], the nitric oxide cycle-related pathways of this tumor [12], the current trends and complications of partial and radical nephrectomy in CCRCC [13], the characteristics of the intratumor immune heterogeneity in non-metastatic tumors [14], the importance of NPC1 targeting in CCRCC [15], and a comparison between the efficacy of immune checkpoint inhibitors (ICI) and tyrosine kinase inhibitors (TKI)/everolimus in the adjuvant therapy of CCRCC [16].…”

“…In a very interesting article, Fujita et al [6] analyze the association of the tumor immune microenvironment in the primary tumor with the intervals of metastases. For this purpose, the authors considered synchronous (metastases within 3 months) and metachronous (metastases after 3 months) CCRCC in a series of 568 patients.…”