Lymphangiogenesis predicts favorable outcomes to immunotherapy

Reviewed by Emily Henderson, B.Sc.Jun 8 2021

Oncotarget published "Mutually exclusive lymphangiogenesis or perineural infiltration in human skin squamous-cell carcinoma" which reported that although tumor-associated lymphangiogenesis correlates with metastasis and poor prognosis in several cancers, it also supports T cell infiltration into the tumor and predicts favorable outcome to immunotherapy.

Using quantitative multiplex immunohistochemistry, the authors analyzed skin squamous-cell carcinoma (sSCC) sections from 36 patients.

CD8 T cell infiltration showed great differences between patients, whereby these cells were mainly excluded from the tumor mass. Similar to our data in melanoma, sSCC with high density of lymphatic endothelial cells showed increased CD8 T cell density in tumor areas.

An entirely new observation is that sSCC with perineural infiltration but without metastasis was characterized by low lymphatic endothelial cell density.

Since both metastasis and perineural infiltration are known to affect tumor progression and patients' prognosis, it is important to identify the molecular drivers, opening future options for therapeutic targeting. This Oncotarget data suggest that the mechanisms underlying perineural infiltration may be linked with the biology of lymphatic vessels and thus stroma.

Over the last few years, oncology research is increasingly focused on the understanding of mutual interactions between cancer, stromal and immune cells in the tumor microenvironment."

Dr. Karin Schaeuble, The University Hospital Lausanne

Specific growth factors like vascular endothelial growth factor -C and -D secreted by tumor cells and/or immune cells stimulate lymphangiogenesis in the vicinity of the tumor.

Lymphatic vessels offer a route for cancer cells to disseminate, enhanced by secretion of different chemokines such as CCL21 that actively supports tumor cell invasion into lymphatic vessels and promotes lymph node metastases.

Investigations into the immune cell composition showed the presence of various immune cells in sSCC.

On the other hand, the presence of lymphatic vessels in the tumour immune microenvironment (TME) has also been shown to support adaptive anti-tumoral immune responses by carrying immune cells and antigens to the draining LNs.

For further investigation of possible associations of lymphatic vessels with stroma and T cells, they performed a comprehensive analysis of the abundance and localization of lymphatic vessels in 36 patients with sSCC.

The Schaeuble Research Team concluded in their Oncotarget Research Output that an entirely new observation is that perineural infiltrated sSCC in absence of metastases are characterized by low LVD compared to tumors without PNI.

Since both are known to affect tumor progression and patients' prognosis, it may be particularly important to identify the underlying mechanisms triggering either lymphangiogenesis or PNI, thus opening future options for therapeutic targeting.