The Tumor Immune Microenvironment in Cutaneous Squamous Cell Carcinoma Arising in Organ Transplant Recipients

Zilberg, Catherine; Lyons, J. Guy; Gupta, Ruta; Ferguson, Angela; Damian, Diona L.

doi:10.5021/ad.22.175

Cited by 5 publications

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

A combined opposite targeting of p110δ PI3K and RhoA abrogates skin cancer

Tzenaki,

Xenou,

Goulielmaki

et al. 2024

Commun Biol

View full text Add to dashboard Cite

Malignant melanoma is the most aggressive and deadly skin cancer with an increasing incidence worldwide whereas SCC is the second most common non-melanoma human skin cancer with limited treatment options. Here we show that the development and metastasis of melanoma and SCC cancers can be blocked by a combined opposite targeting of RhoA and p110δ PI3K. We found that a targeted induction of RhoA activity into tumours by deletion of p190RhoGAP-a potent inhibitor of RhoA GTPase-in tumour cells together with adoptive macrophages transfer from δD910A/D910A mice in mice bearing tumours with active RhoA abrogated growth progression of melanoma and SCC tumours. Τhe efficacy of this combined treatment is the same in tumours lacking activating mutations in BRAF and in tumours harbouring the most frequent BRAF(V600E) mutation. Furthermore, the efficiency of this combined treatment is associated with decreased ATX expression in tumour cells and tumour stroma bypassing a positive feedback expression of ATX induced by direct ATX pharmacological inactivation. Together, our findings highlight the importance of targeting cancer cells and macrophages for skin cancer therapy, emerge a reverse link between ATX and RhoA and illustrate the benefit of p110δ PI3K inhibition as a combinatorial regimen for the treatment of skin cancers.

show abstract

A combined opposite targeting of p110δ PI3K and RhoA abrogates skin cancer

Tzenaki,

Xenou,

Goulielmaki

et al. 2024

Commun Biol

View full text Add to dashboard Cite

show abstract

Rapid Life-Saving Response to Anti–PD-1 in a Solid Organ Transplant Recipient With Metastatic Cutaneous Squamous Cell Carcinoma: A Case Report and Review

Antonelli,

Quach,

Mahajan

et al. 2024

Journal of Immunotherapy

View full text Add to dashboard Cite

Summary Anti–programmed cell death protein 1 (PD-1) therapy is considered effective in the treatment of metastatic or locally advanced cutaneous squamous cell carcinoma but the use of these agents in solid organ transplant recipients (SOTRs) is often taken with caution. While anti-tumor effects without graft rejection have been reported, studies have shown high rates of fatal graft rejection with immune checkpoint therapy. In this case report, we present an SOTR patient with life-threatening, acute hypoxic respiratory failure due to rapidly progressive metastatic cutaneous squamous cell carcinoma with lung and pleural involvement. Modification of their immunosuppressive regimen and treatment with front-line anti–PD-1 inhibitor, pembrolizumab, led to rapid clinical response with near complete resolution of metastatic pulmonary disease and no long-term evidence of graft rejection. Our case report shows that front-line treatment with PD-1 inhibitors can be safely administered in SOTR patients with rapid metastatic disease control.

show abstract

Induced B-Cell Receptor Diversity Predicts PD-1 Blockade Immunotherapy Response

Che,

Lee,

Abou-Taleb

et al. 2024

Preprint

View full text Add to dashboard Cite

Immune checkpoint inhibitors such as anti-PD-1 antibodies (aPD1) can be effective in treating advanced cancers. However, many patients do not respond and the mechanisms underlying these differences remain incompletely understood. In this study, we profile a cohort of patients with locally-advanced or metastatic basal cell carcinoma undergoing aPD-1 therapy using singlecell RNA sequencing, high-definition spatial transcriptomics in tumors and draining lymph nodes, and spatial immunoreceptor profiling, with long-term clinical follow-up. We find that successful responses to PD-1 inhibition are characterized by an induction of B-cell receptor (BCR) clonal diversity after treatment initiation. These induced BCR clones spatially co-localize with T-cell clones, facilitate their activation, and traffic alongside them between tumor and draining lymph nodes to enhance tumor clearance. Furthermore, we validated aPD1-induced BCR diversity as a predictor of clinical response in a larger cohort of glioblastoma, melanoma, and head and neck squamous cell carcinoma patients, suggesting that this is a generalizable predictor of treatment response across many types of cancers. We discover that pre-treatment tumors harbor a characteristic gene expression signature that portends a higher probability of inducing BCR clonal diversity after aPD-1 therapy, and we develop a machine learning model that predicts PD-1-induced BCR clonal diversity from baseline tumor RNA sequencing. These findings underscore a dynamic role of B cell diversity during immunotherapy, highlighting its importance as a prognostic marker and a potential target for intervention in non-responders.

show abstract

The Tumor Immune Microenvironment in Cutaneous Squamous Cell Carcinoma Arising in Organ Transplant Recipients

Cited by 5 publications

References 54 publications

A combined opposite targeting of p110δ PI3K and RhoA abrogates skin cancer

A combined opposite targeting of p110δ PI3K and RhoA abrogates skin cancer

Rapid Life-Saving Response to Anti–PD-1 in a Solid Organ Transplant Recipient With Metastatic Cutaneous Squamous Cell Carcinoma: A Case Report and Review

Induced B-Cell Receptor Diversity Predicts PD-1 Blockade Immunotherapy Response

Contact Info

Product

Resources

About