FOSL2 promotes intertumoral infiltration of T cells and increases pathological complete response rates in locally advanced rectal cancer patients

Xu, Kailun; Yin, Xiang; Zhou, Biting; Zheng, Xiaojiao; Wang, Hao; Chen, Jing; Cai, Xue; Gao, Huanhuan; Xu, Xiao–Ming; Wang, Liuhong; Shen, Li; Guo, Tiannan; Zheng, Shu; Li, Baosheng; Shao, Yingkuan; Wang, Jian

doi:10.1016/j.canlet.2023.216145

Cited by 3 publications

(4 citation statements)

References 53 publications

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“…It should also be considered that in breast tumors, the paths to a complete pathological response follow the activation of numerous pathways other than apoptosis such as the activation of the immune response. Activation of the PI3K/AKT/MTOR pathway acts by decreasing the action of FOX01, BCL-2 and their proapoptosis activity and is another pathway of drug resistance [49,50]. This knowledge of drug resistance pathways makes it possible to develop drugs with specific action that induce a better response.…”

Section: Discussionmentioning

confidence: 99%

<i>TP53</i> Gene Polymorphism at Codon 72 as a Response Predictor for Neoadjuvant Chemotherapy

Vieira,

Pesquero,

Nazário

2024

Breast Care

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Introduction: Breast cancer is one of the most prevalent cancers in women worldwide and neoadjuvant chemotherapy is a favored method for achieving pathologic complete response (pCR). The TP53 gene is involved in inducing the response to chemotherapy drugs. Objectives: The present study sought to correlate polymorphism variants at codon 72 with pathologic complete response to neoadjuvant chemotherapy. Casuistry and Methods: The study was conducted in the state of Sergipe, in Northeastern Brazil. A total of 206 patients with a histopathological diagnosis of breast cancer who underwent neoadjuvant chemotherapy from 2019 to 2022 were included. DNA samples were collected for the evaluation of TP53 polymorphism at codon 72. A prospective evaluation of the cases was conducted to verify the surgical pathologic response after chemotherapy; the response evaluation criteria in solid tumors were used (RECIST). The study was approved by the University of São Paulo Ethics and Research Committee. Results: Of the 168 patients, 44.6% were Arg72Arg, 17.3% Pro72Pro, and 38.0% Arg72Pro; pCR was achieved in 21.4% of the patients; 10.1% had progressive disease, 13.7% stable disease, and 54.2% had a partial pathologic response. The only predictor of pCR in multivariate regression was immunohistochemistry (p < 0.001). In the multivariate analysis, Arg72Pro and Pro72Pro increased the odds of the patient evolve with stable disease.This study was innovative in demonstrating a predictor of stable disease in response to neoadjuvant chemotherapy Conclusion: TP53 polymorphism at codon 72 is not a predictor of pathologic complete response, but it can be a predictor of stable disease.

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Section: Discussionmentioning

confidence: 99%

<i>TP53</i> Gene Polymorphism at Codon 72 as a Response Predictor for Neoadjuvant Chemotherapy

Vieira,

Pesquero,

Nazário

2024

Breast Care

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“… 16 Higher levels of CXCL10 in tumors are associated with better prognoses in non-small cell lung cancer 17 , 18 and rectal cancer. 19 Consequently, increasing CXCL10 secretion in the TME may be a pivotal strategy to potentially boost the recruitment of CXCR3+ immune cells (T and NK cells). Studies have demonstrated that methods such as induced tumor cell secretion, 20 fusion proteins, 21 and small-molecule RORγt agonists 22 can effectively elevate CXCL10 levels, thereby enhancing recruitment signals and promoting the aggregation of immune cells.…”

Section: Introductionmentioning

confidence: 99%

CXCL10 and IL15 co-expressing chimeric antigen receptor T cells enhance anti-tumor effects in gastric cancer by increasing cytotoxic effector cell accumulation and survival

Nie,

Song,

et al. 2024

OncoImmunology

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Chimeric antigen receptor (CAR) T cells have demonstrated outstanding therapeutic success in hematological malignancies. Yet, their efficacy against solid tumors remains constrained due to inadequate infiltration of cytotoxic T and CAR-T cells in the tumor microenvironment (TME), a factor correlated with poor prognosis in patients with solid tumors. To overcome this limitation, we engineered CAR-T cells to secrete CXCL10 and IL15 (10 × 15 CAR-T), which sustain T cell viability and enhance their recruitment, thereby amplifying the long-term cytotoxic capacity of CAR-T cells in vitro. In a xenograft model employing NUGC4-T21 cells, mice receiving 10 × 15 CAR-T cells showed superior tumor reduction and extended survival rates compared to those treated with second-generation CAR-T cells. Histopathological evaluations indicated a pronounced increase in cytotoxic T cell accumulation in the TME post 10 × 15 CAR-T cell treatment. Therefore, the synergistic secretion of CXCL10 and IL15 in these CAR-T cells enhances T cell recruitment and adaptability within tumor tissues, improving tumor control. This approach may offer a promising strategy for advancing CAR-T therapies in the treatment of solid tumors.

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“…However, when the interplay between neoplastic and non-neoplastic cells is considered, the significance of Fra-2 expression drastically changes, since it acts as a critical mediator of sensitivity to therapeutic administration. Indeed, it has been reported that Fra-2 levels positively correlates with CD8 + T cell infiltration and tumor regression in rectal cancer samples from patients treated with chemo-radiotherapy [ 109 ]. Mechanistically, the therapy-induced overexpression of Fra-2 increases CXCL10 secretion and CD8 + T cell recruitment in the TME, enhancing the cytotoxic response against CRC cells [ 109 ].…”

Section: Introductionmentioning

confidence: 99%

“…Indeed, it has been reported that Fra-2 levels positively correlates with CD8 + T cell infiltration and tumor regression in rectal cancer samples from patients treated with chemo-radiotherapy [ 109 ]. Mechanistically, the therapy-induced overexpression of Fra-2 increases CXCL10 secretion and CD8 + T cell recruitment in the TME, enhancing the cytotoxic response against CRC cells [ 109 ].…”

Section: Introductionmentioning

confidence: 99%

Role of Fra-2 in cancer

Rampioni Vinciguerra,

Capece,

Scafetta

et al. 2023

Cell Death Differ

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Fos-related antigen-2 (Fra-2) is the most recently discovered member of the Fos family and, by dimerizing with Jun proteins, forms the activator protein 1 (AP-1) transcription factor. By inducing or repressing the transcription of several target genes, Fra-2 is critically involved in the modulation of cell response to a variety of extracellular stimuli, stressors and intracellular changes. In physiological conditions, Fra-2 has been found to be ubiquitously expressed in human cells, regulating differentiation and homeostasis of bone, muscle, nervous, lymphoid and other tissues. While other AP-1 members, like Jun and Fos, are well characterized, studies of Fra-2 functions in cancer are still at an early stage. Due to the lack of a trans-activating domain, which is present in other Fos proteins, it has been suggested that Fra-2 might inhibit cell transformation, eventually exerting an anti-tumor effect. In human malignancies, however, Fra-2 activity is enhanced (or induced) by dysregulation of microRNAs, oncogenes and extracellular signaling, suggesting a multifaceted role. Therefore, Fra-2 can promote or prevent transformation, proliferation, migration, epithelial-mesenchymal transition, drug resistance and metastasis formation in a tumor- and context-dependent manner. Intriguingly, recent data reports that Fra-2 is also expressed in cancer associated cells, contributing to the intricate crosstalk between neoplastic and non-neoplastic cells, that leads to the evolution and remodeling of the tumor microenvironment. In this review we summarize three decades of research on Fra-2, focusing on its oncogenic and anti-oncogenic effects in tumor progression and dissemination.

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FOSL2 promotes intertumoral infiltration of T cells and increases pathological complete response rates in locally advanced rectal cancer patients

Cited by 3 publications

References 53 publications

<i>TP53</i> Gene Polymorphism at Codon 72 as a Response Predictor for Neoadjuvant Chemotherapy

<i>TP53</i> Gene Polymorphism at Codon 72 as a Response Predictor for Neoadjuvant Chemotherapy

CXCL10 and IL15 co-expressing chimeric antigen receptor T cells enhance anti-tumor effects in gastric cancer by increasing cytotoxic effector cell accumulation and survival

Role of Fra-2 in cancer

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