scholarly journals Case Report: Exceptional Response to Nivolumab Plus Ipilimumab in a Young Woman With TFE3-SFPQ Fusion Translocation-Associated Renal Cell Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Dylan J. Martini ◽  
Caroline S. Jansen ◽  
Lara R. Harik ◽  
Sean T. Evans ◽  
T. Anders Olsen ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
T Cells ◽  
Cell Carcinoma ◽  
Cd8 T Cells ◽  
Renal Cell ◽  
Lymphovascular Invasion ◽  
Checkpoint Inhibitors ◽  
Predictive Biomarkers ◽  
Response To Treatment ◽  
Rare Malignancy

Translocation-associated renal cell carcinoma (tRCC) is a rare, aggressive malignancy that primarily affects children and young adults. There is no clear consensus on the most effective treatment for tRCC and there are no biomarkers of response to treatments in these patients. We present a case of a 23 year-old female with metastatic tRCC to the lungs who was started on treatment with nivolumab and ipilimumab. She had a complete radiographic response to treatment and has been progression-free for over 18 months. Immunofluorescence imaging performed on the baseline primary tumor sample showed significant intratumoral immune infiltration. Importantly, these cells are present in niches characterized by TCF1+ CD8+ T cells. Histopathologic investigation showed the presence of lymphocytes in the fibrovascular septae and foci of lymphovascular invasion. Furthermore, lymphovascular invasion and intratumor niches with TCF1+ CD8+ T cells may predict a favorable response to treatment with nivolumab and ipilimumab. These findings have significant clinical relevance given that immune checkpoint inhibitors are approved for several malignancies and predictive biomarkers for response to treatment are lacking. Importantly, the identification of these TCF1+ CD8+ T cells may guide treatment for patients with tRCC, which is a rare malignancy without a consensus first-line treatment option.

scholarly journals Multidiscipline Immunotherapy-Based Rational Combinations for Robust and Durable Efficacy in Brain Metastases from Renal Cell Carcinoma

2021 ◽  
Vol 22 (12) ◽  
pp. 6290
Author(s):  
Hye-Won Lee
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Imaging Techniques ◽  
Predictive Biomarkers ◽  
Effective Control ◽  
Extrinsic Factors ◽  
Medical Needs

Advanced imaging techniques for diagnosis have increased awareness on the benefits of brain screening, facilitated effective control of extracranial disease, and prolonged life expectancy of metastatic renal cell carcinoma (mRCC) patients. Brain metastasis (BM) in patients with mRCC (RCC-BM) is associated with grave prognoses, a high degree of morbidity, dedicated assessment, and unresponsiveness to conventional systemic therapeutics. The therapeutic landscape of RCC-BM is rapidly changing; however, survival outcomes remain poor despite standard surgery and radiation, highlighting the unmet medical needs and the requisite for advancement in systemic therapies. Immune checkpoint inhibitors (ICIs) are one of the most promising strategies to treat RCC-BM. Understanding the role of brain-specific tumor immune microenvironment (TIME) is important for developing rationale-driven ICI-based combination strategies that circumvent tumor intrinsic and extrinsic factors and complex positive feedback loops associated with resistance to ICIs in RCC-BM via combination with ICIs involving other immunological pathways, anti-antiangiogenic multiple tyrosine kinase inhibitors, and radiotherapy; therefore, novel combination approaches are being developed for synergistic potential against RCC-BM; however, further prospective investigations with longer follow-up periods are required to improve the efficacy and safety of combination treatments and to elucidate dynamic predictive biomarkers depending on the interactions in the brain TIME.

Tumor-infiltrating CD8+ T cells recognize a heterogeneously expressed functional neoantigen in clear cell renal cell carcinoma

2021 ◽  
Author(s):  
Masahiro Matsuki ◽  
Yoshihiko Hirohashi ◽  
Munehide Nakatsugawa ◽  
Aiko Murai ◽  
Terufumi Kubo ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
T Cells ◽  
Cell Carcinoma ◽  
Cd8 T Cells ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma

scholarly journals Determinants of anti-PD1 response and resistance in clear cell renal cell carcinoma

2021 ◽  
Author(s):  
Lewis Au ◽  
Emine Hatipoglu ◽  
Marc Robert de Massy ◽  
Kevin Litchfield ◽  
Andrew Rowan ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
T Cells ◽  
Cell Carcinoma ◽  
Cd8 T Cells ◽  
Renal Cell ◽  
Clear Cell ◽  
Endogenous Retrovirus ◽  
Human Endogenous Retrovirus ◽  
Cell Renal Cell Carcinoma ◽  
Pre Treatment

Antigen recognition and T-cell mediated cytotoxicity in clear-cell renal cell carcinoma (ccRCC) remains incompletely understood. To address this knowledge gap, we analysed 115 multiregion tumour samples collected from 15 treatment-naive patients pre- and post-nivolumab therapy, and at autopsy in three patients. We performed whole-exome sequencing, RNAseq, TCRseq, multiplex immunofluorescence and flow cytometry analyses and correlated with clinical response. We observed pre-treatment intratumoural TCR clonal expansions suggesting pre-existing immunity. Nivolumab maintained pre-treatment expanded, clustered TCR clones in responders, suggesting ongoing antigen-driven stimulation of T-cells. T-cells in responders were enriched for expanded TCF7+CD8+ T-cells and upregulated GZMK/B upon nivolumab-binding. By contrast, nivolumab promoted accumulation of new TCR clones in non-responders, replacing pre-treatment expanded clonotypes. In this dataset, mutational features did not correlate with response to nivolumab and human endogenous retrovirus expression correlated indirectly. Our data suggests that nivolumab potentiates clinical responses in ccRCC by binding pre-existing expanded CD8+ T-cells to enhance cytotoxicity.

scholarly journals Tim-3 Expression on Tumor-Infiltrating PD-1+CD8+ T Cells Correlates with Poor Clinical Outcome in Renal Cell Carcinoma

2016 ◽  
Vol 77 (5) ◽  
pp. 1075-1082 ◽  
Author(s):  
Clémence Granier ◽  
Charles Dariane ◽  
Pierre Combe ◽  
Virginie Verkarre ◽  
Saïk Urien ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
T Cells ◽  
Clinical Outcome ◽  
Cell Carcinoma ◽  
Cd8 T Cells ◽  
Renal Cell ◽  
Poor Clinical Outcome

scholarly journals Renal Cell Carcinoma in the Era of Precision Medicine: From Molecular Pathology to Tissue-Based Biomarkers

2018 ◽  
Vol 36 (36) ◽  
pp. 3553-3559 ◽  
Author(s):  
Sabina Signoretti ◽  
Abdallah Flaifel ◽  
Ying-Bei Chen ◽  
Victor E. Reuter
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Checkpoint Inhibitors ◽  
Predictive Biomarkers ◽  
Molecular Features ◽  
Pathologic Features ◽  
Clear Cell Rcc ◽  
Metastatic Rcc

Renal cell carcinoma (RCC) is not a single entity but includes various tumor subtypes that have been identified on the basis of either characteristic pathologic features or distinctive molecular changes. Clear cell RCC is the most common type of RCC and is characterized by dysregulation of the von Hippel Lindau/hypoxia-inducible factor pathway. Non–clear cell RCC represents a more heterogeneous group of tumors with diverse histopathologic and molecular features. In the past two decades, the improved understanding of the molecular landscape of RCC has led to the development of more effective therapies for metastatic RCC, which include both targeted agents and immune checkpoint inhibitors. Because only subsets of patients with metastatic RCC respond to a given treatment, predictive biomarkers are needed to guide treatment selection and sequence. In this review, we describe the key histologic features and molecular alterations of RCC subtypes and discuss emerging tissue-based biomarkers of response to currently available therapies for metastatic disease.

scholarly journals Clinical importance of the expression of CD4+CD8+ T cells in renal cell carcinoma

2020 ◽  
Vol 32 (5) ◽  
pp. 347-357 ◽  
Author(s):  
Kentaro Nishida ◽  
Atsunari Kawashima ◽  
Takayuki Kanazawa ◽  
Yujiro Kidani ◽  
Tetsuya Yoshida ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
T Cells ◽  
Cell Carcinoma ◽  
Rna Sequencing ◽  
Cd8 T Cells ◽  
Renal Cell ◽  
Clinical Importance ◽  
Cancer Types ◽  
Prognostic Importance ◽  
Infiltrating Lymphocytes

Abstract Objective CD4+CD8+ T cells are expressed in some cancer patients including those with renal cell carcinoma (RCC). However, no reports have mentioned the clinical importance of this expression. We evaluated the expression of CD4+CD8+ T cells in patients with various cancer types to clarify clinical characteristics and prognostic importance significantly correlating with these T cells. Methods Expression of CD4+CD8+ T cells was evaluated using flowcytometry in tissue-infiltrating lymphocytes extracted from 260 cancer tissues including 104 RCC samples. RNA sequencing and characterization and regression (Citrus) was used to determine characteristics. The prognostic importance of CD4+CD8+ T cells was evaluated by Cox regression analysis. Results Among eight cancer types, expression of CD4+CD8+ T cells was significantly highest in RCC patients. According to the expression of CD4+CD8+ T cells in adjacent normal tissue-infiltrating lymphocytes, 24 patients (23.1%) were defined as being positive for CD4+CD8+ with an expression higher than 9.29% in RCC patients. Citrus showed CD8+PD-1+TIM-3+CD103− T cells to be a specific subpopulation of CD4+CD8+ T cells. RNA sequencing revealed that CD4+CD8+ T cells had significantly lower diversity than the other T cells and shared most T-cell receptor clones with CD8+ not CD4+ T cells. Expression of CD4+CD8+ T cells was identified as an independent predictor of overall survival (hazard ratio: 0.11, 95% confidence interval: 0.01–0.86, P = 0.035) in multivariate analysis. Conclusions The expression of CD4+CD8+ T cells was significantly up-regulated in RCC patients and correlated significantly with prognostic importance in surgically treated RCC patients.

Sign in / Sign up

Export Citation Format

Share Document