Infiltration of CD3+ and CD68+ cells in bladder cancer is subtype specific and affects the outcome of patients with muscle-invasive tumors

ObjectivesUrothelial carcinoma (UC) aggressiveness is determined by tumor inherent molecular characteristics, such as molecular subtypes, as well as by host reactions directed toward the tumor. Cell types responsible for the host?s response include tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs). The aim of the present investigation was to explore the immunological response in relation to UC molecular subtypes and to evaluate the prognostic effect of TIL and TAM counts in tissue sections from muscle-invasive (MI) tumors.Methods and materialsTissue microarrays with 296 tumors spanning all pathological stages and grades were analyzed with antibodies for CD3, CD8, FOXP3, CD68, and CD163. Cases were classified into the following molecular subtypes: urobasal, genomically unstable, and squamous cell carcinoma–like using a combination of immunohistochemistry and histology. The Cox regression and Kaplan-Meier analyses were performed with progression-free survival and disease-specific survival as end points.ResultsUC molecular subtypes demonstrate different degrees of immunological responses; the urobasal subtype induces a weak response, the genomically unstable subtype induces an intermediate response, and the squamous cell carcinoma–like subtype induces a strong response. These subtype specific responses are independent of tumor stage and include both TILs and TAMs. The presence of infiltrating CD3⁺ TILs was significantly associated with good prognosis in the MI cases (P<0.01). This positive association was modulated by the presence of CD68⁺ TAMs. The strongest association with poor survival was observed for a high ratio between CD68 and CD3 (P = 7×10^?5).ConclusionUC molecular subtypes induce immunological responses at different levels. A high CD68/CD3 ratio identifies a bad prognosis group among MI UC cases.     

Macrophage density is an adverse prognosticator for ipsilateral recurrence in ductal carcinoma in situ

IntroductionThere is evidence that supports the association of dense tumor infiltrating lymphocyte (TILs) with an increased risk of ipsilateral recurrence in ductal carcinoma in situ (DCIS). However, the association of cellular composition of DCIS immune microenvironment with the histopathologic parameters and outcome is not well understood.MethodsWe queried our institutional database for patients with pure DCIS diagnosed between 2010 and 2019. Immunohistochemical studies for CD8, CD4, CD68, CD163, and FOXP3 were performed and evaluated in the DCIS microenvironment using tissue microarrays. Statistical methods included Fisher's exact test for categorical variables and the two-sample t-test or the Wilcoxon Rank-Sum test for continuous variables.ResultsThe analytic sample included 67 patients. Median age was 62 years (range = 53 to 66) and median follow up was 6.7 years (range = 5.3 to 7.8). Thirteen patients had ipsilateral recurrence. Of all the clinicopathologic variables, only the DCIS size and TIL density were significantly associated with recurrence (p = 0.023 and 0.006, respectively). After adjusting for age and TIL density, only high CD68 (>50) and high CD68/CD163 ratio (>0.46) correlated with ipsilateral recurrence (p = 0.026 and 0.013, respectively) and shorter time to recurrence [hazard ratio 4.87 (95% CI: 1.24–19, p = 0.023) and 10.32 (95% CI: 1.34–80, p = 0.025), respectively].ConclusionsIn addition to DCIS size and TIL density, high CD68⁺ tumor-associated macrophages predict ipsilateral recurrence in DCIS. High CD68⁺ macrophage density and CD68/CD163 ratio also predict a shorter time to recurrence.     

Robust method for isolation of tumor infiltrating lymphocytes with a high vital cell yield from small samples of renal cell carcinomas by a new collagenase-free mechanical procedure

Background

Tumor-infiltrating lymphocytes (TIL) play an important role in the pathogenesis of renal cell carcinoma. Characterization of TIL requires efficient isolation procedures, especially in early stage disease when the tumor is of small in size. Conventional methods for isolating TIL are based on enzymatic tissue digestion, most frequently with collagenase. Collagenase isolation is limited by poor cell recovery, altered expression of cell-surface molecules, and impaired TIL-functionality. To overcome these limitations, we developed and optimized conditions for a robust collagenase-free mechanical procedure for improved isolation of TIL from renal cell carcinoma samples.

Clinical significance of tumor-infiltrating lymphocytes in neoplastic progression and lymph node metastasis of human breast cancer

To investigate the clinical significance of tumor-infiltrating lymphocytes (TILs) within the tumor milieu, we quantitatively measured and compared the subpopulations of TILs in 24 patients with stage I–III breast carcinoma. Peripheral blood mononuclear cells (PBMCs), normal breast parenchyma-infiltrating lymphocytes (NILs), and TILs were isolated from tissue specimens and quantified by flow cytometry. The results showed that increased proportion of CD8⁺ T cells, with decreased proportion of CD4⁺ T cells, was significant in gated CD3⁺ TILs as compared to autologous NILs or PBMCs (P < 0.001). The tumor-infiltrating CD8⁺ T cells significantly increased with stage progression, reflected in a more strongly decreased CD4/CD8 percentage (P = 0.003). The CD4/CD8 percentage of TILs was strongly correlated with lymphovascular permeation and subsequent lymph node metastasis (P < 0.001). Increased percentages of tumor-infiltrating CD8⁺ T cells with decreased CD4/CD8 percentages are of prognostic importance for cancer progression in human breast cancer.     

Detection and Functional Analysis of Tumor Infiltrating T-Lymphocytes (TIL) in Liver Metastases from Colorectal Cancer

Background  Tumor-infiltrating T lymphocytes (TIL) play an important role in primary colorectal cancer, but their activity in liver metastases has not yet been investigated. The aim of this study was to examine whether tumor-selective infiltration, activation, and cytotoxic activity of TIL can be demonstrated in situ in colorectal liver metastases. Methods  TIL were obtained from liver metastases and corresponding normal liver tissue of 16 patients with colorectal liver metastases. Characterization of TIL in situ was performed by multicolor flowcytometric analysis. Presence of tumor antigen-reactive T cells was evaluated by interferon gamma Elispot analysis. Results  TIL in colorectal liver metastases responding against tumor antigens were present in most patients. Although the proportions of CD3⁺ T cells were comparable in liver metastasis and normal liver tissue, metastases contained significantly enhanced proportions of CD4⁺ cells (49% vs. 22%, P < .001). Among all CD4⁺ T helper cells, the proportion of activated (CD4⁺CD25⁺) effector cells was significantly increased in liver metastases (15.0% vs. 7.8%, P = .003). Metastases showed significantly higher proportions of activated (CD69⁺ [70.1% vs. 49.8%, P = .02] and CD25⁺ [4.1% vs. .6%, P = .06]) and cytotoxically active (CD107a⁺) CD8⁺ TIL (3.2% vs. 1.3%, P = .03). Importantly, the presence of activated T helper cells correlated with the frequencies of cytotoxic T lymphocytes that exerted cytotoxic activity in situ (P = .02). Conclusion  CD4⁺ and CD8⁺ TIL are selectively activated in liver metastases, and cytotoxic T lymphocytes exert tumor-selective cytotoxic activity in situ in the presence of activated T helper cells, suggesting the requirement of in-situ-activated T helper cells for efficient cytotoxic T lymphocytes effector function. P. Wagner and M. Koch contributed equally to this study. An erratum to this article can be found at     

CMV specific T cell immune response in hepatitis C negative kidney transplant recipients receiving transplant from hepatitis C viremic donors and hepatitis C aviremic donors

Kidney transplants (KT) from hepatitis C (HCV) viremic donors to HCV negative recipients has shown promising renal outcomes, however, high incidence of cytomegalovirus (CMV) viremia were reported. We performed a prospective cohort study of 52 HCV negative KT recipients from Methodist University Hospital including 41 receiving transplants from HCV aviremic donors and 11 from HCV viremic donors. CMV specific CD4+ and CD8 + T cell immunity was measured by intracellular flow cytometry assay. Primary outcome was the development of positive CMV specific CD4+ and CD8 + T cell immune response in the entire cohort and each subgroup. The association between donor HCV status and CMV specific CD4+ and CD8 + T cell immune response was analyzed by Cox proportional hazard models. Mean recipient age was 48 ± 13 years, with 73% male and 82% African American. Positive CMV specific CD4+ and CD8 + T cell immune response was found in 53% and 47% of the cohort at 1 month, 65% and 70% at 2 months, 80% and 75% at 4 months, 89% and 87% at 6 months, and 94% and 94% at 9 months post-transplant, respectively. There was no significant difference in the incidence of positive CMV specific T cell immune response between recipients of transplants from HCV aviremic donors compared to HCV viremic donors in unadjusted (for CD8+: HR = 1.169, 95%CI: 0.521–2.623; for CD4+: HR = 1.208, 95%CI: 0.543–2.689) and adjusted (for CD8+: HR = 1.072, 95%CI: 0.458–2.507; for CD4+: HR = 1.210, 95%CI: 0.526–2.784) Cox regression analyses. HCV viremia in donors was not associated with impaired development of CMV specific T cell immunity in this cohort.     

The pulmonary arterial hypertension of patients on maintained hemodialysis is positively associated with the decreased percent of CD8 T cell in the peripheral blood independently

Objective To explore the risk factors of pulmonary artery hypertension (PAH) and the its relationship with T cell subsets to provide a foundation for the prevention and treatment of PAH. Methods 154 maintained hemodialysis (MHD) patients in our dialysis center were recruited according to the criterion and divided into two groups subsequently: PAH group (pulmonary artery systolic pressure, PASP＞35 mmHg) and non-PAH group (PASP≤35 mmHg). The related clinical, biochemical and ultrasonic cardiogram data were collected and peripheral blood was acquired to detect the expressions of the surface antigen CD3, CD4, CD8 and CD69 with flow cytometry. Logistic regression analysis was used to find out the relationship between PAH and T cell subsets. Results There was no significant difference between 56 cases of PAH and 98 cases of non-PAH as regards gender, age, mean systolic and diastolic pressure, dialysis durations, morbidities of hypertension and diabetes, smoking rate, and left ventricular diameter. Compared with the non?PAH group, the PAH group demonstrated a lower percent of CD8 T cells and CD8 CD69 T cells, but a much higher left atrial diameter (LAD), Interventricular septum thickness, left ventricular posterior wall thickness, and NT?proBNP. The percentage of T cells, CD4 T cells and CD4 CD69 T cells showed no difference between the two groups. Multivariate analysis confirmed that PAH was negatively independently associated with the percentage of CD8 T cells and CD8CD69 T cells. Conclusions The decreased percentage of CD8 T cells and CD8CD69 T cells in the peripheral blood is a risk factor of PAH in maintained hemodialysis patients, and CD8 T cells may play an important role in the genesis of PAH.     

Peripheral Versus Intraparenchymal Papillary Thyroid Microcarcinoma: Different Morphologies and PD-L1 Expression

Peripheral localisation of papillary thyroid microcarcinoma (PTMC), in comparison with intraparenchymal PTMC (i-PTMC) is related to some clinicopathological features related with biological aggressiveness, including lymph node metastasis (LNM). The expression of PD-L1 in tumour cell has been associated with increased tumour survival, progression, and potentially an aggressive clinical course. This study evaluates the relation between clinicopathological features of PTMC, including tumour localisation, with PD-L1 immunoexpression. The study included 99 patients with the histological diagnosis of PTMC (≥ 5 mm). PD-L1 protein expression was assessed by immunohistochemistry. PTMCs were divided into the four following groups: G1– peripherally localised PTMC (p-PTMC) with PD-L1 expression; G2–p-PTMC without PD-L1 expression; G3–i-PTMC with PD-L1 expression and G4–i-PTMC without PD-L1 expression. G1 was the most frequent (n = 46; 46.5%), followed by G4 (n = 25; 25.3%) and similar distribution of G3 (n = 15; 15.2%) and G2 (n = 13; 13.1%). In comparison with other groups, G1 was significantly associated with classical morphology, invasive growth, lymphatic invasion (LI), vascular invasion (VI), psammoma bodies, intratumoral fibrosis, PD-L1 positive tumour-infiltrating lymphocytes, and multinuclear giant cells (MGCs). G4 more commonly exhibited follicular morphology, expansive/circumscribed growth, and absence of the following: intratumoural fibrosis, LI, VI, psammoma bodies, PD-L1 positive tumour-infiltrating lymphocytes, and MGCs. LNMs were significantly more frequent in G1 in comparison with the other groups (p = 0.000). In conclusion, morphology and tumour microenvironment of p-PTMC with PD-L1 expression is different from i-PTMC without PD-L1 expression. The differences between these two groups of PTMC include clinicopathological features related with biological aggressiveness such as the occurrence of LNM.     

肿瘤浸润性淋巴细胞对乳腺癌患者细胞免疫功能的影响

目的 探讨肿瘤浸润性淋巴细胞（TIL）对乳腺癌患者细胞免疫功能的影响及临床意义。方法 从肿瘤组织分离培养的TIL,对25例乳腺癌患者进行治疗,检测治疗前后T淋巴细胞亚群、自然杀伤细胞（NK细胞）活性及血清可溶性白介素－2受体（sIL-2R)水平的变化。结果 经TIL治疗后患者外周血CD3、CD4、CD4／CD8和NK细胞活性均明显增高,CD8、sIL-2R水平明显降低。结论 TIL能提高乳腺癌患者的细胞免疫功能。     

Improved in vivo efficacy of tumor-infiltrating lymphocytes after restimulation with irradiated tumor cells in vitro

Background: We investigated different culture conditions for tumor-infiltrating lymphocytes (TILs) with regard to proliferation, phenotypic changes, in vitro cytotoxicity, and in vivo therapeutic efficacy. Methods: After enzymatic digestion of the murine fibrosarcoma, MCA-105, TIL cultures were initiated as pure lymphocyte (groups 1 and 2) or mixed lymphocyte/tumor suspensions (groups 3 and 4). Group 1 TILs were grown in culture medium containing 100 IU/ml recombinant interleukin-2 (rIL-2). Group 2 TILs were stimulated with solid-phase anti-CD3 monoclonal antibody (mAb) for 48 h and cultured in rIL-2 (100 IU/ml)-containing medium. Group 3, which consisted initially of a surplus of tumor cells, received the same treatment as group 2. Group 4 was also activated with anti-CD3 mAb and rIL-2 but was additionally restimulated weekly with irradiated tumor cells (TILs to tumor, 20:1). Results: Groups 1 and 2 showed up to twofold higher increases in TIL numbers compared with groups 3 and 4 by the end of culture week 5. Although the original lymphocyte/tumor cell suspension consisted of 12.0 ± 3.8% CD4⁺ T cells and 5.3 ± 3.3% CD8⁺ T cells, all four TIL cultures showed 80% CD8⁺ TILs and no CD4⁺ TILs by the end of culture week 4. In vitro cytotoxicity did not correlate with in vivo efficacy of the examined TIL cultures. By using the MCA-105 pulmonary metastases model in C57BL/6 mice, only suboptimal doses of TILs (2 × 10⁶) from group 4, which had been restimulated weekly with irradiated tumor, showed significant tumor eradication compared with all other treatment groups (p<0.01). Conclusions: We conclude that in vitro tumor restimulation of TILs improves in vivo efficacy, most likely through the education of tumor-reactive T cells.Presented at the 48th Annual Meeting of The Society of Surgical Oncology, Boston, Massachusetts, March 23–26, 1995.     

Tumor-infiltrating lymphocytes derived from human renal cell carcinoma: Clonal analysis of its characteristics

Aim:   To assess the characteristics of activated tumor-infiltrating lymphocytes (TIL), we report the isolation, growth response, and functional analysis of a CD4^- CD8⁺ TIL-clone derived from human renal cell carcinoma (RCC).
Methods:   Bulk TILs were expanded from a human RCC and the lymphocytes were separated into a CD8⁺ enriched population. Subsequently, using the limiting dilution technique, a TIL clone was established and its growth response, phenotype and cytotoxic activity were analyzed.
Results:   A clone, T16-13, by day 94 numbering 1 × 10⁷ cells, was harvested and characterized as a CD4^- CD8⁺ clone. On day 144, the cytotoxic activity of this clone against the autologous tumor was relatively high (2.3 ± 0.7 LU₃₀/10⁶ cells). Meanwhile, against allogeneic renal tumors, there was no cytotoxic activity (−0.1 LU₃₀/10⁶ cells).
Conclusions:   A TIL clone possessing modest autologous tumor-specific cytotoxicity can be isolated from human RCC. The characteristics analysis of various TIL clones may provide a better understanding of an RCC tumor microenvironment and may help to establish new modalities for the treatment of patients with metastatic kidney cancer.     

Donor‐Specific CD8+Foxp3+ T Cells Protect Skin Allografts and Facilitate Induction of Conventional CD4+Foxp3+ Regulatory T Cells

CD4⁺ regulatory T cells play a critical role in tolerance induction in transplantation. CD8⁺ suppressor T cells have also been shown to control alloimmune responses in preclinical and clinical models. However, the exact nature of the CD8⁺ suppressor T cells, their induction and mechanism of function in allogeneic transplantation remain elusive. In this study, we show that functionally suppressive, alloantigen‐specific CD8⁺Foxp3⁺ T cells can be induced and significantly expanded by stimulating naïve CD8⁺ T cells with donor dendritic cells in the presence of IL‐2, TGF‐β1 and retinoic acid. These CD8⁺Foxp3⁺ T cells express enhanced levels of CTLA‐4, CCR4 and CD103, inhibit the up‐regulation of costimulatory molecules on dendritic cells, and suppress CD4 and CD8 T cell proliferation and cytokine production in a donor‐specific and contact‐dependent manner. Importantly, upon adoptive transfer, the induced CD8⁺Foxp3⁺ T cells protect full MHC‐mismatched skin allografts. In vivo, the CD8⁺Foxp3⁺ T cells preferentially traffic to the graft draining lymph node where they induce conventional CD4⁺Foxp3⁺ T cells and concurrently suppress effector T cell expansion. We conclude that donor‐specific CD8⁺Foxp3⁺ suppressor T cells can be induced and exploited as an effective form of cell therapy for graft protection in transplantation.     

Tim-3 expression represents dysfunctional tumor infiltrating T cells in renal cell carcinoma

Purpose

Renal cell carcinoma (RCC) is the most common cancer of kidney. Evidences have shown that RCC is sensitive to various immunotherapies. Tim-3 plays a role in suppressing Th1-mediated immune responses. However, no study has yet examined the effect of Tim-3 on tumor infiltrating lymphocytes (TILs) in RCC.

Methods

We investigated the expression and function of Tim-3 on TIL CD4+ T cells and TIL CD8+ T cells from 30 RCC patients.

Results

Levels of Tim-3 were significantly increased on both TIL CD4+ T cells and TIL CD8+ T cells and were associated with higher stages of the cancer. Also, GATA-3 and interferon gamma (IFN-γ) were down-regulated, whereas T-bet was up-regulated in TIL Tim-3+ T cells, indicating that Tim-3 expression defined a population of dysfunctional TIL Th1/Tc1 cells. Mechanism analyses showed that TIL Tim-3-expressing CD8+ T cells exhibited impaired Stat5 and p38 signaling pathway. Blocking the Tim-3 pathway restored cell proliferation and increased IFN-γ production in TIL CD4+ and CD8+ T cells of RCC.

Conclusions

These results suggest that Tim-3 may be used as a novel target for increasing immune responses in RCC tumor microenvironment.

     

Prognostic factor analysis for patient outcome of PD-L1 expression in thoracic oesophageal squamous cell carcinoma

Open in a separate window OBJECTIVESThe purpose of this study was to determine the expression of PD-L1 in oesophageal squamous cell carcinoma (OSCC) and the prognostic factors.METHODSPD-L1 expression was investigated by immunohistochemical staining of resected specimens from 50 OSCC patients who were randomly selected from 104 patients with complete follow-up data. The relationships among PD-L1 expression, clinicopathological factors and prognosis were assessed by statistical analysis.RESULTSThe expression of PD-L1 was positive in 27 (54%, positive cells’ proportion > 25%) and negative in 23 (46%, positive cells proportion ≤25%) of 50 cases, and PD-L1 expression was negative in all pericarcinomatous tissues (P > 0.05). The 5-year survival rate of patients with PD-L1-positive expression was 22.2% (6 of 27), which was less than that of patients with PD-L1-negative expression (47.8%; 11 of 23) (P < 0.05). The results showed significant differences in the depth of tumour invasion, lymph node status, postoperative pathological stage and PD-L1 expression (P < 0.05). Multivariable analysis showed that PD-L1 expression was an independent prognostic factor for survival.CONCLUSIONSThe depth of tumour invasion, lymph node status, postoperative pathological stage and PD-L1 expression are important factors affecting the prognosis of patients with thoracic OSCC; in particular, high PD-L1 expression was a significant independent poor prognostic factor in thoracic OSCC patients.     

膀胱癌TIL的分离培养及其表型分析

对３例膀胱移行细胞病患者手术切除的肿瘤组织中肿瘤浸浸润性淋巴细胞进行了体外分离与培养，结果２例获得成功，ＴＩＬ体外扩增培数分别达５８－１７０，在培养２４ｄ时对自体肿瘤靶细胞的最高杀伤活性达４１％以上，且呈现一定的靶细胞特异性。     

Anti-PD-L1/TGFβR2 (M7824) fusion protein induces immunogenic modulation of human urothelial carcinoma cell lines,rendering them more susceptible to immune-mediated recognition and lysis

Background

Avelumab has recently been approved by the Food and Drug Administration for the therapy of Merkel cell carcinoma and urothelial carcinoma. M7824 is a novel first-in-class bifunctional fusion protein comprising a monoclonal antibody against programmed death-ligand 1 (PD-L1, avelumab), fused to the extracellular domain of human transforming growth factor beta (TGFβ) receptor 2, which functions as a TGFβ “trap.” Advanced urothelial tumors have been shown to express TGFβ, which possesses immunosuppressive properties that promote cancer progression and metastasis. The rationale for a combined molecule is to block the PD-1/PD-L1 interaction between tumor cells and immune cell infiltrate and simultaneously reduce or eliminate TGFβ from the tumor microenvironment. In this study, we explored the effect of M7824 on invasive urothelial carcinoma cell lines.

FOXP3 and survival in urinary bladder cancer

What's known on the subject? and What does the study add? This is the first study examining FOXP3 expression in invasive urothelial urinary bladder cancer and in their tumour‐infiltrating lymphocytes (TILs). The relation of their respective immunohistological expression to survival adds new knowledge in the fields of tumour immunology and prognostic markers.

OBJECTIVE

? To investigate the possible impact of FOXP3 expression in T‐cells, as well as in tumour cells, on long‐term survival in patients with urinary bladder cancer (UBC) invading muscle.

PATIENTS AND METHODS

? In a retrospective study, tumour specimens from 37 patients cystectomized for T1–T4 UBC during 1999–2002 at the Karolinska University Hospital were examined by immunohistochemistry for tumour expression and/or infiltration of immune cells expressing FOXP3 as well as CD3. ? The results obtained were correlated with clinicopathological parameters, where the primary and secondary outcomes investigated were overall survival and progression‐free survival, respectively.

RESULTS

? Infiltration of CD3⁺ and FOXP3⁺ lymphocytes (≥3 cells per high‐power field) were both correlated with better survival, and this relationship persisted throughout the whole study period (all P < 0.05). ? Patients with FOXP3⁺ tumour cells had decreased long‐term survival compared to those patients with FOXP3^? tumours (P < 0.05). ? Despite a limited amount of patient material, the results of the present study indicate that FOXP3 expression, in both lymphocytes and tumour cells, is an important prognostic factor in UBC.

CONCLUSIONS

? FOXP3 expression in UBC cells is associated with decreased long‐term survival and thus may be a novel negative prognostic factor in UBC invading muscle. ? By contrast, the presence of FOXP3⁺ tumour‐infiltrating lymphocytes was correlated with a positive prognosis. Because FOXP3 is up‐regulated upon activation in human T‐cells, FOXP3 may serve more as an activation marker than as a regulatory T‐cell indicator in this case. ? These results support the need for larger prospective studies aiming to confirm the results obtained and to examine the underlying mechanisms in detail.     

Prognostic value of PD-1 and PD-L1 expression in patients with metastatic clear cell renal cell carcinoma

Objective

In renal cell carcinoma (RCC), several prognostic biomarkers have been identified and are under investigation. Several reports have shown that the expression of programmed death 1 (PD-1) and its ligand PD-L1 is associated with poor outcome for patients with RCC. The present study is aimed at evaluating the expression of PD-1 and PD-L1 and to investigate their clinical and prognostic significance in patients with clear cell RCC (CCRCC) having received molecular targeted therapies. In addition, we also evaluated the relationship between the expression of PD-1 and PD-L1 and intratumoral tumor infiltrating lymphocytes (TILs).

Prognostic value of peripheral blood T lymphocyte subsets in clear cell renal cell carcinoma

BackgroundTo date, few studies have evaluated the role of peripheral blood T lymphocyte subsets in patients with clear cell renal cell carcinoma (ccRCC). Here we measured the levels of peripheral blood T lymphocyte subsets and evaluated its prognostic value in ccRCC.MethodsData from 122 patients with RCC from January 2018 to January 2020 were collected. Preoperative peripheral blood T lymphocyte subsets and medical records were analyzed. Kaplan-Meier cures and log rank test were used for analyzing overall survival (OS). Univariate and multivariate survival analyses were underwent by performing the Cox proportional hazards models. Correlations were tested by Pearson’s correlation analysis.ResultsOf 122 patients, a total of 80 ccRCC patients was enrolled. Patients with low CD3⁺ T cells and low CD4⁺/CD8⁺ ratio displayed a worse OS than patients with high CD3⁺ T cells and high CD4⁺/CD8⁺ ratio (P=0.029 and 0.002, respectively). Multivariate analyses showed CD3⁺ T cells and CD4⁺/CD8⁺ ratio were independent predictive factors for the OS (HR: 0.295, 95% CI, 0.091–0.956; P=0.042 and HR: 0.244, 95% CI, 0.065–0.920; P=0.037, respectively). Moreover, NLR negatively correlated with both levels of CD3⁺ T cells and CD4⁺/CD8⁺ ratio (P<0.001, r=−0.398 and P=0.012, r=−0.280, respectively).ConclusionsThe findings of our study suggest that preoperative CD3⁺ T cells and CD4⁺/CD8⁺ ratio in peripheral blood are independent predictors for patients with ccRCC.