International Urology and Nephrology | 2021
Comment on “Prognostic value of immunological profile based on CD8+\u2009and FoxP3+\u2009T lymphocytes in the peritumoral and intratumoral subsites for renal cell carcinoma”
Abstract
We read with great interest the article by Teke et al. [1] about assessing the prognostic effect of immunological profile including CD8+ and FoxP3+ T lymphocytes at the peritumoral normal and intratumoral tissues for renal cell carcinoma (RCC) in a previous issue of the journal. This immunological profile was shown as a good predictive marker for progression-free survival (PFS). As the critical role of host immune system in controlling tumor progression is better understood, clinical trials investigating various immunological markers with prognostic significance have rapidly increased [2]. In the last 2 years, there has been an increase in studies that create immune profiles using various cellular immunity elements (e.g. CD3+ , CD8+ , FoxP3+ tumor-infiltrating lymphocytes, PD-L1+, and PD-1+ cells). All these studies aim to better predict oncological outcomes by integrating immunoscores into the TNM-staging system [1, 2, 4, 5]. Teke et al. [1] should be congratulated for a well-designed study on this important topic. However, I would like to contribute to their study with some comments. First, clear cell RCC (ccRCC) and non-clear cell RCC (non-ccRCC) have different histopathological and prognostic properties. NonccRCC also consists of various tumors with heterogeneous characteristics. Based on clinical studies on RCC, the oncological outcomes of targeted therapies for metastatic nonccRCC are poorer than ccRCC [3, 7]. In our recent study investigating this topic (but differently assessing CD8+ and CD3+ T lymphocytes at the intratumoral tissue and the invasive margin), the preliminary results for ccRCC have showed that a favorable immunoscore (I3–4) combined with TNM stage and WHO/ISUP 2016 grade could predict better diseasefree survival (DFS), PFS and overall survival (OS) [2]. In our additional report for non-ccRCC, favorable immunoscore (I3–4), lower pathological TNM stage and lower WHO/ISUP 2016 grade were found to be associated with prolonged OS, whereas we could not observe the significant prognostic effect of immunoscore on DFS and PFS [8]. Additionally, we observed that the predictive effect of immunoscore on OS was slightly higher in ccRCC compared to non-ccRCC (HR 2.933 vs. 1.705) [2, 8]. We consider that it would be better to analyze the effect of immune profile on survival for ccRCC and nonccRCC separately. Six (14.2%) patients had papillary RCC in the study of Teke et al. [1]. Although the number of patients is low, the rate of 14.2% is compatible with the proportion of papillary tumors in all RCC population. Therefore, their inclusion may have statistically affected the study outcomes. Second, the WHO/ISUP 2016 grading classification has been validated for clear cell and papillary RCC, and it has now replaced the Fuhrman grading system [7]. Although Teke et al. [1] have mentioned WHO/ISUP 2016 classification in the methods paragraphy, the data of Fuhrman grade were used in the tables. This situation creates confusion. If Fuhrman grade was used, this may have affected the study outcomes. Although a common consensus has been established in the immunoscore classification for colorectal cancers [6], there are some differences in RCC studies in terms of type of immune cells and evaluated tissues [1, 2, 4, 5, 8]. It appears that there is a need to establish a consensus on immune profile for RCC under the guidance of all these aforementioned studies. * Ismail Selvi [email protected]