# Sarcomatoid Renal Cell Carcinoma: Biological Features and Therapeutic Implications—A Narrative Review **Authors:** Francesco Lasorsa, Martina Milella, Monica Rutigliano, Antonio di Bari, Antonio d’Amati, Savio Domenico Pandolfo, Gabriele Bignante, Alessandro Caniglia, Riccardo Autorino, Pasquale Ditonno, Giuseppe Lucarelli PMC · DOI: 10.1007/s11934-026-01325-4 · 2026-03-07 ## TL;DR This paper reviews the aggressive kidney cancer subtype sarcomatoid renal cell carcinoma, focusing on its biology and potential for immunotherapy treatment. ## Contribution The paper provides a comprehensive overview of sRCC's molecular and immune features, suggesting immunotherapy as a promising treatment approach. ## Key findings - sRCC has a highly inflamed tumor microenvironment linked to better response to immunotherapy. - Genomic alterations and immune profiles of sRCC are distinct from other renal cancer subtypes. - Immunotherapy integration may improve outcomes for sRCC patients. ## Abstract This review underscores the importance of recognizing sarcomatoid features in renal cell carcinoma, as this component significantly impacts prognosis and treatment strategies. Sarcomatoid renal cell carcinoma (sRCC) is a rare and aggressive form of renal cancer characterized by poor prognosis and distinct biological features. Despite its clinical significance, there remains a knowledge gap regarding the comprehensive understanding of its molecular and therapeutic landscape. Recent studies provided an extensive overview of the clinical, pathological, and molecular characteristics of sRCC, highlighting its unique genomic alterations and immune profile. Notably, sRCC exhibits a highly inflamed tumor microenvironment, which correlates with increased responsiveness to immune checkpoint inhibitors. Our findings suggest that integrating immunotherapy into the management of sRCC could enhance patient outcomes, paving the way for future research and clinical applications in this challenging cancer subtype. ## Linked entities - **Diseases:** sarcomatoid renal cell carcinoma (MONDO:0003012), renal cell carcinoma (MONDO:0005086) ## Full-text entities - **Genes:** IL15RA (interleukin 15 receptor subunit alpha) [NCBI Gene 3601] {aka CD215}, ARPC5 (actin related protein 2/3 complex subunit 5) [NCBI Gene 10092] {aka ARC16, IMD113, dJ127C7.3, p16-Arc}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, BAP1 (BRCA1 associated deubiquitinase 1) [NCBI Gene 8314] {aka HUCEP-13, KURIS, TPDS1, UBM2, UCHL2, UVM2}, HIF1A (hypoxia inducible factor 1 subunit alpha) [NCBI Gene 3091] {aka HIF-1-alpha, HIF-1A, HIF-1alpha, HIF1, HIF1-ALPHA, MOP1}, IL9 (interleukin 9) [NCBI Gene 3578] {aka HP40, IL-9, P40}, CDH1 (cadherin 1) [NCBI Gene 999] {aka Arc-1, BCDS1, CD324, CDHE, ECAD, LCAM}, MLANA (melan-A) [NCBI Gene 2315] {aka MART-1, MART1}, CALR (calreticulin) [NCBI Gene 811] {aka CALR1, CRT, HEL-S-99n, RO, SSA, cC1qR}, ARPC5L (actin related protein 2/3 complex subunit 5 like) [NCBI Gene 81873] {aka ARC16-2, ARPC5B}, IFI16 (interferon gamma inducible protein 16) [NCBI Gene 3428] {aka IFNGIP1, PYHIN2}, SLC2A1 (solute carrier family 2 member 1) [NCBI Gene 6513] {aka CSE, DYT17, DYT18, DYT9, EIG12, GLUT}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, MUC1 (mucin 1, cell surface associated) [NCBI Gene 4582] {aka ADMCKD, ADMCKD1, ADTKD2, CA 15-3, CD227, Ca15-3}, CDCA7 (cell division cycle associated 7) [NCBI Gene 83879] {aka ICF3, JPO1}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, PSME2 (proteasome activator subunit 2) [NCBI Gene 5721] {aka PA28B, PA28beta, REGbeta}, DES (desmin) [NCBI Gene 1674] {aka CDCD3, CSM1, CSM2, LGMD1D, LGMD1E, LGMD2R}, CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, SNAI1 (snail family transcriptional repressor 1) [NCBI Gene 6615] {aka SLUGH2, SNA, SNAH, SNAIL, SNAIL1, dJ710H13.1}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, CDKN2B (cyclin dependent kinase inhibitor 2B) [NCBI Gene 1030] {aka CDK4I, INK4B, MTS2, P15, TP15, p15INK4b}, ACTB (actin beta) [NCBI Gene 60] {aka BKRNS, BNS, BRWS1, CSMH, DDS1, PS1TP5BP1}, TAP2 (transporter 2, ATP binding cassette subfamily B member) [NCBI Gene 6891] {aka ABC18, ABCB3, APT2, D6S217E, MHC1D2, PSF-2}, LAG3 (lymphocyte activating 3) [NCBI Gene 3902] {aka CD223}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, HIVEP3 (HIVEP zinc finger 3) [NCBI Gene 59269] {aka KBP-1, KBP1, KRC, SHN3, Schnurri-3, ZAS3}, IFI35 (interferon induced protein 35) [NCBI Gene 3430] {aka IFP35}, PAX8 (paired box 8) [NCBI Gene 7849] {aka PAX-8}, TWIST1 (twist family bHLH transcription factor 1) [NCBI Gene 7291] {aka ACS3, BPES2, BPES3, CRS, CRS1, CSO}, MME (membrane metalloendopeptidase) [NCBI Gene 4311] {aka CALLA, CD10, CMT2T, NEP, SCA43, SFE}, NF2 (NF2, moesin-ezrin-radixin like (MERLIN) tumor suppressor) [NCBI Gene 4771] {aka ACN, BANF, SCH, SWNV, merlin-1}, ALK (ALK receptor tyrosine kinase) [NCBI Gene 238] {aka ALK1, CD246, NBLST3}, CTLA4 (cytotoxic T-lymphocyte associated protein 4) [NCBI Gene 1493] {aka ALPS5, CD, CD152, CELIAC3, CTLA-4, GRD4}, CDC6 (cell division cycle 6) [NCBI Gene 990] {aka CDC18L, HsCDC18, HsCDC6, MGORS5}, CDCA3 (cell division cycle associated 3) [NCBI Gene 83461] {aka GRCC8, TOME-1, TOME1}, CDH2 (cadherin 2) [NCBI Gene 1000] {aka ACOGS, ADHD8, ARVD14, CD325, CDHN, CDw325}, TP63 (tumor protein p63) [NCBI Gene 8626] {aka AIS, B(p51A), B(p51B), EEC3, KET, LMS}, PSMA5 (proteasome 20S subunit alpha 5) [NCBI Gene 5686] {aka PSC5, ZETA}, PSMB4 (proteasome 20S subunit beta 4) [NCBI Gene 5692] {aka HN3, HsN3, PRAAS3, PROS-26, PROS26}, CXCL9 (C-X-C motif chemokine ligand 9) [NCBI Gene 4283] {aka CMK, Humig, MIG, SCYB9, crg-10}, CDKN2A (cyclin dependent kinase inhibitor 2A) [NCBI Gene 1029] {aka ARF, CAI2, CDK4I, CDKN2, CMM2, INK4}, CDC45 (cell division cycle 45) [NCBI Gene 8318] {aka CDC45L, CDC45L2, MGORS7, PORC-PI-1}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, CDK6 (cyclin dependent kinase 6) [NCBI Gene 1021] {aka MCPH12, PLSTIRE}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, PAX2 (paired box 2) [NCBI Gene 5076] {aka FSGS7, PAPRS, PAX-2}, PSMC2 (proteasome 26S subunit, ATPase 2) [NCBI Gene 5701] {aka MSS1, Nbla10058, RPT1, S7}, ANLN (anillin, actin binding protein) [NCBI Gene 54443] {aka FSGS8, Scraps, scra}, FOXP3 (forkhead box P3) [NCBI Gene 50943] {aka AIID, DIETER, IPEX, JM2, PIDX, XPID}, EZH2 (enhancer of zeste 2 polycomb repressive complex 2 subunit) [NCBI Gene 2146] {aka ENX-1, ENX1, EZH2b, KMT6, KMT6A, WVS}, CCNE1 (cyclin E1) [NCBI Gene 898] {aka CCNE, pCCNE1}, CA9 (carbonic anhydrase 9) [NCBI Gene 768] {aka CAIX, MN}, TAP1 (transporter 1, ATP binding cassette subfamily B member) [NCBI Gene 6890] {aka ABC17, ABCB2, APT1, D6S114E, MHC1D1, PSF-1}, CDCA8 (cell division cycle associated 8) [NCBI Gene 55143] {aka BOR, BOREALIN, DasraB, MESRGP}, S100A4 (S100 calcium binding protein A4) [NCBI Gene 6275] {aka 18A2, 42A, CAPL, FSP1, MTS1, P9KA}, AMACR (alpha-methylacyl-CoA racemase) [NCBI Gene 23600] {aka AMACRD, CBAS4, P504S, RACE, RM}, VIM (vimentin) [NCBI Gene 7431], PSMB10 (proteasome 20S subunit beta 10) [NCBI Gene 5699] {aka IMD121, LMP10, MECL1, PRAAS5, beta2i}, CCNB1 (cyclin B1) [NCBI Gene 891] {aka CCNB} - **Diseases:** ARON-1 (MESH:C538557), primary renal smooth muscle neoplasms (MESH:D018235), necrosis (MESH:D009336), primary renal sarcomas (MESH:C536413), RCC (MESH:D002292), lymph node metastasis (MESH:D008207), PEComa (MESH:D054973), mRCC (MESH:C538445), chromophobe RCCs (MESH:D000238), sarcomatoid and rhabdoid (MESH:D018335), metastases (MESH:D009362), death (MESH:D003643), thyroid-like follicular carcinoma (MESH:D018263), Renal cancers (MESH:D007680), Hypoxia (MESH:D000860), sarcomatoid adrenocortical carcinoma (MESH:D018268), hemorrhage (MESH:D006470), fibrosarcoma (MESH:D005354), Cancer (MESH:D009369), rearranged (MESH:D002869), malignant mixed epithelial and stromal tumor (MESH:D002277), pelvis (MESH:D010386), angiomyolipoma (MESH:D018207), dedifferentiated liposarcoma (MESH:D008080) - **Chemicals:** Nivolumab (MESH:D000077594), gemcitabine (MESH:D000093542), tryptophan (MESH:D014364), citrate (MESH:D019343), glutamine (MESH:D005973), lipid (MESH:D008055), lenvatinib (MESH:C531958), capecitabine (MESH:D000069287), Pembrolizumab (MESH:C582435), fatty acid (MESH:D005227), CN (-), everolimus (MESH:D000068338), ipilimumab (MESH:D000074324), sorafenib (MESH:D000077157), glutamate (MESH:D018698), bevacizumab (MESH:D000068258), sunitinib (MESH:D000077210), iron (MESH:D007501), Cabozantinib (MESH:C558660), atezolizumab (MESH:C000594389), tricarboxylic acid (MESH:D014233), Avelumab (MESH:C000609138), axitinib (MESH:D000077784) - **Species:** Homo sapiens (human, species) [taxon 9606] - **Cell lines:** ARON-1 — Mus musculus (Mouse), Hybridoma (CVCL_C7RB) ## Figures 1 figure with captions in the complete paper: https://tomesphere.com/paper/PMC12966250/full.md --- Source: https://tomesphere.com/paper/PMC12966250