multiplex-immunohistochemical-analysis-spatial-immune-cell-landscape

Multiplex Immunohistochemical Analysis of the Spatial Immune Cell Landscape of the Tumor Microenvironment

The immune cell landscape of the tumor microenvironment potentially contains information for the discovery of prognostic and predictive biomarkers. ...

Radboudumc

Radboud University

Whereas neoadjuvant cisplatin-based chemotherapy (NAC) followed by a radical cystectomy remains the standard treatment for patients with muscle-invasive bladder cancer (MIBC), increasing evidence suggests that checkpoint inhibitors, either alone or in combination with chemotherapy, are effective in the (neo)adjuvant setting. The major aim of this study was to improve our understanding of the immune-modulating effects of NAC in MIBC.

Intratumoral T cell depletion following neoadjuvant chemotherapy in patients with muscle-invasive bladder cancer is associated with poor clinical outcome.

Homologous recombination repair deficiency (HRD) is observed in 10% of patients with castrate-resistant prostate cancer (PCa). Preliminary data suggest that HRD-PCa might be more responsive to immune checkpoint inhibitors (ICIs). In this study, we compare the tumor immune landscape and peripheral T cell receptor (TCR) repertoire of patients with and without HRD-PCa to gain further insight into the immunogenicity of HRD-PCa. Immunohistochemistry was performed on tumor tissue of 81 patients, including 15 patients with HRD-PCa. Peripheral TCR sequencing was performed in a partially overlapping cohort of 48 patients, including 16 patients with HRD-PCa. HRD patients more frequently had intratumoral CD3, CD3CD8FoxP3 or Foxp3 TILs above median compared to patients without DNA damage repair alterations (DDRwt; CD3 and Foxp3: 77% vs 35%, p = .013; CD3CD8FoxP3: 80% vs 44%, p = .031). No significant difference in CD8 TILs or PD-L1 expression was observed. In peripheral blood, HRD patients displayed a more diverse TCR repertoire compared to DDRwt patients (p = .014). Additionally, HRD patients shared TCR clusters with low generation probability, suggesting patient-overlapping T cell responses. A pooled analysis of clinical data from 227 patients with molecularly characterized PCa suggested increased efficacy of ICIs in HRD-PCa. In conclusion, patients with HRD-PCa display increased TIL density and an altered peripheral TCR repertoire. Further research into the efficacy of ICIs and the presence of shared neoantigens in HRD-PCa is warranted.

Article	Year
Intratumoral T cell depletion following neoadjuvant chemotherapy in patients with muscle-invasive bladder cancer is associated with poor clinical outcome. Cancer immunology, immunotherapy : CII\| PubMed ID: 35771253	2023
Homologous recombination repair deficient prostate cancer represents an immunologically distinct subtype. Oncoimmunology\| PubMed ID: 35800157	2022

Shabaz Sultan

Biography

JoVE Journal Publications

Other Publications