Dados do Resumo

Título

Spatial organization and functional characterization of immune cells in the tumor microenvironment of endometrial cancer patients as a strategy for unraveling new immunotherapeutic targets

Introdução

Endometrial cancer (EC) is one of the most common gynecological cancers. In cancer patients, the immune cells are more prone to become exhausted and ineffective in eliminating the tumor. Recently, immune checkpoint inhibitors, especially anti-PD1, have shown to be effective in reinvigorating the cytotoxic function of CD8+ T cells. However, about 75% of EC patients do not respond to this therapy. It is known that the immune response is more efficient when organized in cellular aggregates, such as tertiary lymphoid structures (TLS), due to optimal cell communication and induction of robust immune responses.

Objetivo

Our work aims to characterize lymphocyte organization and communication within TLS and its clinical relevance in EC patients.

Métodos

To accomplish this, we analyzed sixteen tumor, peri-tumoral, and blood samples from patients recruited at A.C. Camargo Hospital.
Tissue samples were disassociated with a collagenase solution, and the cell suspension obtained was analyzed by flow cytometry. Tissue slides were analyzed by immunohistochemistry.

Resultados

In tumor samples, conventional and regulatory (Treg) CD4 T cells, as well as CD8 T cells, showed a cell phenotype indicative of tumor reactivity, characterized by a higher expression of activation (CD39 and CD69), tissue-resident (CD103) and exhaustion (PD-1) markers compared to peri-tumoral and blood samples. Analysis of public endometrial scRNAseq and scTCRseq data showed that T cells expressing this phenotype, together with CXCL13 expression, are organized within TLS and undergo clonal expansion, further supporting that these cells are tumor reactive. Furthermore, tissue slides from our cohort showed intra-tumoral lymphocyte aggregates in most patients, indicating potential TLS formation. Besides, CD4 Treg, but not conventional, is increased in the tumor tissue compared to blood samples. We are conducting additional experiments to evaluate whether Tregs are also allocated within intra-tumoral TLS.

Conclusões

Overall, our results reveal potential interactions between different immune cell populations within lymphocyte aggregates that can be key to boost antitumor response.

Financiador do resumo

CAPES, CNPq e FAPESP

Palavras Chave

immune reponse; tertiary lymphoid structures; endometrial cancer