# Can oral squamous cell carcinoma xenografts tumors mirror the original tumor microenvironment? An immunohistochemical analysis

**Authors:** Mateus José Dutra, Brendo Vinicius Rodrigues Louredo, Sebastião Silvério de Sousa-Neto, Hélen Kaline Farias Bezerra, Ana Carolina Prado-Ribeiro, Leandro Luongo Matos, Felipe Martins Silveira, Manoela Domingues Martins, Luiz Paulo Kowalski, Pablo Agustin Vargas, Vivian Petersen Wagner

PMC · DOI: 10.1007/s00428-026-04399-0 · Virchows Archiv · 2026-01-27

## TL;DR

This study compares the tumor microenvironment in oral cancer xenograft models to the original tumors and finds some features are preserved while others change.

## Contribution

The study reveals that certain TME markers are preserved in PDX models while others, like immune cell markers, are significantly reduced.

## Key findings

- Histological grade of PDX tumors showed instability across passages.
- Expression of SMA, claudin-1, vimentin, and Ki-67 was maintained in PDX tumors.
- CD4, CD8, CD31, and CD34 expression was significantly reduced in PDX tumors compared to original tumors.

## Abstract

This study aimed to characterize the tumor microenvironment (TME) in patient-derived xenograft (PDX) models of oral squamous cell carcinoma (OSCC) and compare histological findings with primary tumors of origin (PTT). OSCC samples from five donor patients were implanted into NOD/SCID mice (PDX0) and subsequently re-implanted into new animals (PDX1), yielding three groups for analysis: PTT, PDX0, and PDX1 (n = 5 each). Histological slides with sections were stained with hematoxylin and eosin for grade analysis and subjected to immunohistochemical reactions with antibodies against SMA, CD4, CD8, CD31, CD34, Claudin-1, Vimentin, and Ki-67. Multiple comparisons were performed between samples (PTT, PDX0, and PDX1). The histological grade of PDX0 and PDX1 tumors showed instability across passages. The expression of SMA, claudin-1, vimentin, and Ki-67 was maintained, with no significant differences between PDX0 and PDX1 when compared with PTT. In contrast, the expression of CD4, CD8, CD31, and CD34 was significantly reduced in PDX0 and PDX1 tumors compared with PTT. OSCC PDX tumors may exhibit instability in the degree of differentiation compared with the donor tumors across passages, as well as alterations in certain components of the TME, including cancer-associated fibroblasts, epithelial–mesenchymal transition–related features, and cellular proliferation characteristics.

The online version contains supplementary material available at 10.1007/s00428-026-04399-0.

## Linked entities

- **Proteins:** SMN1 (survival of motor neuron 1, telomeric), CD4 (CD4 molecule), CD8A (CD8 subunit alpha), PECAM1 (platelet and endothelial cell adhesion molecule 1), CD34 (CD34 molecule), CLDN7 (claudin 7), PRELID1 (PRELI domain containing 1), Mki67 (antigen identified by monoclonal antibody Ki 67)
- **Diseases:** oral squamous cell carcinoma (MONDO:0004958)

## Full-text entities

- **Genes:** PECAM1 (platelet and endothelial cell adhesion molecule 1) [NCBI Gene 5175] {aka CD31, CD31/EndoCAM, GPIIA', PECA1, PECAM-1, endoCAM}, CLDN1 (claudin 1) [NCBI Gene 9076] {aka CLD1, ILVASC, SEMP1}, VIM (vimentin) [NCBI Gene 7431], CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, SMN1 (survival of motor neuron 1, telomeric) [NCBI Gene 6606] {aka BCD541, GEMIN1, SMA, SMA1, SMA2, SMA3}, CD34 (CD34 molecule) [NCBI Gene 947], CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}
- **Diseases:** cancer (MESH:D009369), OSCC (MESH:D000077195), SCID (MESH:D053632), NOD (MESH:D020191)
- **Species:** Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090]

## Full text

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## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12963117/full.md

## References

1 references — full list in the complete paper: https://tomesphere.com/paper/PMC12963117/full.md

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Source: https://tomesphere.com/paper/PMC12963117