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Case Reports
. 2021 Dec 16:11:793808.
doi: 10.3389/fonc.2021.793808. eCollection 2021.

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

Dylan J Martini  1   2 , Caroline S Jansen  2   3 , Lara R Harik  4 , Sean T Evans  2   5 , T Anders Olsen  2   5 , Viraj A Master  3 , Haydn T Kissick  3 , Mehmet Asim Bilen  2
Affiliations
Case Reports

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

Dylan J Martini et al. Front Oncol. .

Abstract

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.

Keywords: TCF1+ CD8+ T cells; combination immune checkpoint therapy; exceptional responder; intratumoral immune niche; rare malignancy; translocation-associated RCC.

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Conflict of interest statement

MB has acted as a paid consultant for and/or as a member of the advisory boards of Exelixis, Bayer, BMS, Eisai, Pfizer, AstraZeneca, Janssen, Calithera Biosciences, Genomic Health, Nektar, and Sanofi and has received grants to his institution from Xencor, Bayer, Bristol-Myers Squibb, Genentech/Roche, Seattle Genetics, Incyte, Nektar, AstraZeneca, Tricon Pharmaceuticals, Genome & Company, AAA, Peloton Therapeutics, and Pfizer for work performed as outside of the current study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Pathology and Histology Samples (A) Gross kidney specimen demonstrating a superior pole multi-nudular, well-defined yellow cream mass with areas of hemorrhagic degeneration and necrosis. (B) Histologic examination shows solid nests of polygonal clear cells with prominent neclei with nucleoli. The intervening fibrovascular septae contain small lymphocytic infiltrates (black arrows). (C) Unique intra-cytoplasmic melanin pidment which may be seen in melanotic translocation-associated renal cell carcinoma (black arrows). (D) The carcinoma was positive for HMB45, a melanocytic marker which can be positive in melantonic translocation-associated renal cell carcinoma.
Figure 2
Figure 2
(A) Immunofluorescence imaging (40x, tiled) demonstrates the presence of intratumoral immune niches containing CD8+ and MHC-11+ cells. Nuclei are stained with DAPI. (B) Immunofluorescence imaging (40x) demonstrates the presence of TCF 1+ CD8+ T cells in MHC-11+ antigen presenting cell dense niches. Nuclei are stained with DAPI.
See this image and copyright information in PMC

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