Prognostic role of proliferating CD8+ cytotoxic Tcells in human cancers

Abstract Purpose Expansion of CD8+ cytotoxic Tlymphocytes is a prerequisite for anti-cancer immune activity and has gained interest in the era of immune checkpoint therapy. Methods To understand the CD8+ T cell dynamics in the tumor microenvironment, we used multiplex fluorescence immunohistochemistry to quantitate CD8+ proliferation (Ki67 co-expression) in tissue microarrays from 1107 colorectal, 642 renal cell, 1066 breast, 375 ovarian, 451 pancreatic and 347 gastric cancer samples. Results The density and the percentage of proliferating (Ki67+) CD8+ T cells were both highly variable between tumor types as well as between patients with the same tumor type. Elevated density and percentage of proliferating CD8+ cytotoxic T cells were significantly associated with favorable tumor parameters such as low tumor stage, negative nodal stage (p ≤ 0.0041 each), prolonged overall survival (p ≤ 0.0028 each) and an inflamed immune phenotype (p = 0.0025) in colorectal cancer and, in contrast, linked to high tumor stage, advanced ISUP/Fuhrman/Thoenes grading (each p ≤ 0.003), shorter overall survival (p ≤ 0.0330 each) and an immune inflamed phenotype (p = 0.0094) in renal cell cancer. In breast, ovarian, pancreatic and gastric cancer the role of (Ki67+)CD8+ Tcells was not linked to clinicopathological data. Conclusion Our data demonstrate a tumor type dependent prognostic impact of proliferating (Ki67+)CD8+ Tcells and an inverse impact in colorectal and renal cell cancer.

Download Full-text

Phase II Study of Erlotinib in Patients With Locally Advanced or Metastatic Papillary Histology Renal Cell Cancer: SWOG S0317

Journal of Clinical Oncology ◽

10.1200/jco.2008.18.8821 ◽

2009 ◽

Vol 27 (34) ◽

pp. 5788-5793 ◽

Cited By ~ 69

Author(s):

Michael S. Gordon ◽

Michael Hussey ◽

Raymond B. Nagle ◽

Primo N. Lara ◽

Philip C. Mack ◽

...

Keyword(s):

Overall Survival ◽

Treatment Failure ◽

Disease Control ◽

Survival Time ◽

Renal Cell Cancer ◽

Renal Cell ◽

Cell Cancer ◽

Single Agent ◽

Locally Advanced ◽

Tumor Type

Purpose Patients with advanced papillary renal cell cancer (pRCC) have poor survival after systemic therapy; the reported median survival time is 7 to 17 months. In this trial, we evaluated the efficacy of erlotinib, an oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor in patients with advanced pRCC, a tumor type associated with wild-type von Hippel Lindau gene. Patients and Methods Patients with histologically confirmed, advanced, or metastatic pRCC were treated with erlotinib 150 mg orally once daily. A RECIST (Response Evaluation Criteria in Solid Tumors) response rate (RR) of ≥ 20% was considered a promising outcome. Secondary end points included overall survival and 6-month probability of treatment failure. Results Of 52 patients registered, 45 were evaluable. The overall RR was 11% (five of 45 patients; 95% CI, 3% to 24%), and the disease control rate was 64% (ie five partial response and 24 stable disease). The median overall survival time was 27 months (95% CI, 13 to 36 months). Probability of freedom from treatment failure at 6 months was 29% (95% CI, 17% to 42%). There was one grade 5 adverse event (AE) of pneumonitis, one grade 4 thrombosis, and nine other grade 3 AEs. Conclusion Although the RECIST RR of 11% did not exceed prespecified estimates for additional study, single-agent erlotinib yielded disease control and survival outcomes of interest with an expected toxicity profile. The design of future trials of the EGFR axis in pRCC should be based on preclinical or molecular data that define appropriate patient subgroups, new drug combinations, or potentially more active alternative schedules.

Download Full-text

CD98hc (SLC3A2), a novel biomarker correlating with grade of malignancy in renal cell cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e15083 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e15083-e15083

Author(s):

Marina Pöttler ◽

Andrea Aaitel ◽

Manuela Schmidinger ◽

Christoph Zielinski ◽

Gerald Prager

Keyword(s):

Renal Cell Cancer ◽

Renal Cell ◽

Cell Cancer ◽

Tumor Stage ◽

Prognostic Impact ◽

Expression Levels ◽

Tnm System ◽

Grade Of Malignancy ◽

Reliable Marker ◽

Grade 3

e15083 Background: In a variety of malignant diseases certain malignant markers either predict treatment response towards systemic therapies or have a prognostic impact for cancer patients. While a variety of such actionable as well as treatable targets have been characterized, although only in certain cancers, in renal cell cancer (RCC) no prognostic markers have so far been identified. Thus, grading according to the S.A. Fuhrman grading system from 1982 is the only prognostic feature and currently widely considered for treatment assessment. Methods: Paraffin-embedded tumor tissue sections derived from clear cell RCCs were immuno-histochemically analyzed for expression of embryonic transmembrane antigen CD98hc (SLC3A2). Expression levels were semi-quantitative analyzed and results were correlated with grade of differentiation, using the widely accepted Fuhrman classification. Results: We found that grade of malignancy of ccRCCs were directly correlated with high CD98hc expression levels. Semi-quantivative analyses revealed that 0 % (0/2) of grade 1 ccRCC, 70.0 % of grade 2 ccRCC (14/20), 86.6 % of grade 3 (26/30) and 100 % of grade 4 (10/10) were CD98hc positive. (p < 0.01, Qui-Quadrat Pearson test, n = 62). In contrast, tumor stage as determined by the WHO TNM system did not correlate with CD98hc levels (p > 0.05). Conclusions: From these data, we conclude that CD98hc is expressed in RCCs, whereby the extent of expression is likely to correlate directly with grade of malignancy. In ccRCCs, CD98hc might represent a novel and reliable marker for more aggressive and less differentiated subtypes.

Download Full-text

Toxicities of axitinib, sunitinib and temsirolimus: implications for progression-free and overall survival in metastatic renal cell cancer

Future Oncology ◽

10.2217/fon-2020-0900 ◽

2020 ◽

Author(s):

Annemarie Uhlig ◽

Johannes Uhlig ◽

Lutz Trojan ◽

Michael Woike ◽

Marianne Leitsmann ◽

...

Keyword(s):

Overall Survival ◽

Cancer Patients ◽

Skin Reaction ◽

Renal Cell Cancer ◽

Renal Cell ◽

Cell Cancer ◽

Progression Free Survival ◽

Cox Models ◽

Metastatic Renal Cell Cancer ◽

Hand Foot Skin Reaction

The aim of this study was to evaluate the association between axitinib, sunitinib and temsirolimus toxicities and patient survival in metastatic renal cell cancer patients. Overall survival (OS) and progression-free survival (PFS) of metastatic renal cell cancer patients from the prospective multicenter STAR-TOR study were assessed using multivariable Cox models. A total of 1195 patients were included (n = 149 axitinib; n = 546 sunitinib; n = 500 temsirolimus). The following toxicities significantly predicted outcomes: hand–foot skin reaction (hazard ratio [HR] = 0.29) for PFS with axitinib; stomatitis (HR = 0.62) and pneumonitis (HR = 0.23) for PFS with temsirolimus; stomatitis (HR = 0.52) and thrombocytopenia (HR = 0.6) for OS with temsirolimus; fatigue (HR = 0.71) for PFS with sunitinib; hand–foot skin reaction (HR = 0.56) and fatigue (HR = 0.58) for OS with sunitinib. In conclusion, in metastatic renal cell cancer, axitinib, sunitinib and temsirolimus demonstrate specific toxicities that are protective OS/PFS predictors.

Download Full-text

Emerging role of tyrosine kinase inhibitors in the treatment of advanced renal cell cancer: a review

Annals of Oncology ◽

10.1093/annonc/mdj133 ◽

2006 ◽

Vol 17 (8) ◽

pp. 1185-1196 ◽

Cited By ~ 46

Author(s):

P. Schöffski ◽

H. Dumez ◽

P. Clement ◽

A. Hoeben ◽

H. Prenen ◽

...

Keyword(s):

Tyrosine Kinase ◽

Tyrosine Kinase Inhibitors ◽

Renal Cell Cancer ◽

Renal Cell ◽

Kinase Inhibitors ◽

Cell Cancer ◽

Advanced Renal Cell Cancer

Download Full-text

The role of prostaglandin E2 in renal cell cancer development: future implications for prognosis and therapy

Future Oncology ◽

10.2217/fon.14.152 ◽

2014 ◽

Vol 10 (14) ◽

pp. 2177-2187 ◽

Cited By ~ 12

Author(s):

Katarzyna Kaminska ◽

Cezary Szczylik ◽

Fei Lian ◽

Anna M Czarnecka

Keyword(s):

Prostaglandin E2 ◽

Renal Cell Cancer ◽

Renal Cell ◽

Cell Cancer ◽

Cancer Development

Download Full-text

International renal-cell-cancer study. VI. The role of medical and family history

International Journal of Cancer ◽

10.1002/(sici)1097-0215(19960611)66:6<723::aid-ijc2>3.0.co;2-1 ◽

1996 ◽

Vol 66 (6) ◽

pp. 723-726 ◽

Cited By ~ 57

Author(s):

Brigitte Schlehofer ◽

Wolfgang Pommer ◽

Anders Mellemgaard ◽

John H. Stewart ◽

Margaret McCredie ◽

...

Keyword(s):

Family History ◽

Renal Cell Cancer ◽

Renal Cell ◽

Cell Cancer ◽

Cancer Study

Download Full-text

Nephrectomy Followed by Interferon Alfa-2b Compared With Interferon Alfa-2b Alone for Metastatic Renal Cell Cancer

50 Studies Every Urologist Should Know ◽

10.1093/med/9780190655341.003.0020 ◽

2021 ◽

pp. 113-118

Author(s):

Christopher Weight

Keyword(s):

Renal Cell Carcinoma ◽

Overall Survival ◽

Cell Carcinoma ◽

Metastatic Renal Cell Carcinoma ◽

Renal Cell Cancer ◽

Renal Cell ◽

Performance Status ◽

Cell Cancer ◽

Interferon Alfa ◽

Cytoreductive Nephrectomy

This chapter summarizes the findings of a landmark trial of cytoreductive nephrectomy in patients with metastatic renal cell carcinoma performed in the interferon era. All enrolled patients had a good performance status. It found overall survival extended by about 3 months in the cytoreductive-nephrectomy-plus-interferon arm versus the interferon-only arm.

Download Full-text