Prognostic and Predictive Significance of Stromal Tumor-Infiltrating Lymphocytes (sTILs) in ER-Positive/HER2−Negative Postmenopausal Breast Cancer Patients

Pousette, Jenny; Johansson, Annelie; Jönsson, Carolin; Fornander, Tommy; Lindström, Linda S.; Olsson, Hans; Pérez-Tenorio, Gizeh

doi:10.3390/cancers14194844

Cited by 3 publications

(3 citation statements)

References 55 publications

(83 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Despite this, CD19-positive B cells have been observed to inhibit the aggressiveness of triple-negative breast cancer (TNBC) and the HER2-positive breast cancer subtype, extend patients' lifespans, and reinforce antitumor immunity. 16 Additionally, other studies have demonstrated that CD19(+) B cells prolong the life of those with muscle-invasive bladder cancer. 17 The part of CD19(+) tumor-infiltrating B cells in certain solid tumors is still a matter of contention.…”

Section: Introductionmentioning

confidence: 99%

The Pan-Cancer Analysis Uncovers the Prognostic and Immunotherapeutic Significance of CD19 as an Immune Marker in Tumor

Wei,

Meng,

Xiang

et al. 2024

IJGM

View full text Add to dashboard Cite

Background:The specific cytotoxic effects of anti-CD19 chimeric antigen receptor (CAR) T-cell therapy have led to impressive outcomes in individuals previously treated for B-cell malignancies. However, the specific biological role of CD19(+) target cells, which exert antitumor immunity against some solid tumors, remains to be elucidated. Methods: We collected information regarding the level of CD19 mRNA and protein expression from various databases including The Cancer Genome Atlas (TCGA), Tumor Immune Estimation Resource (TIMER), Genotype-Tissue Expression (GTEx), and Human Protein Atlas (HPA) for both tumor and normal samples. To evaluate the patient's prognosis according to CD19 expression, a Kaplan-Meier (KM) analysis and univariate Cox regression were performed. Furthermore, using the Estimation of Stromal and Immune Cells in Malignant Tumor Tissues Using the Expression Data (ESTIMATE) algorithm, we estimated the ratio of immune cells infiltrating malignant tumor tissues. Afterward, the GSCALite repository was employed to evaluate the vulnerability of tumors expressing CD19 to drugs used in chemotherapy. To validate the results in clinical samples of certain cancer types, immunohistochemistry was then performed. Results: Most tumor types exhibited CD19 expression differently, apart from colon adenocarcinoma (COAD). The early diagnostic value of CD19 has been demonstrated in 9 different tumor types, and the overexpression of CD19 has the potential to extend the survival duration of patients. Multiple tumors showed a positive correlation between CD19 expression and tumor mutation burden (TMB), microsatellite instability (MSI), and ESTIMATE score. Furthermore, a direct association was discovered between the expression of CD19 and the infiltration of immune cells, particularly in cases of breast invasive carcinoma (BRCA). Moreover, CD19 is highly sensitive to a variety of chemotherapy drugs. Conclusion:The study reveals the potential of CD19 as both a predictive biomarker and a target for different cancer immunotherapies.

show abstract

Section: Introductionmentioning

confidence: 99%

The Pan-Cancer Analysis Uncovers the Prognostic and Immunotherapeutic Significance of CD19 as an Immune Marker in Tumor

Wei,

Meng,

Xiang

et al. 2024

IJGM

View full text Add to dashboard Cite

show abstract

“…Similarly, distant recurrence-free interval (DRFI) of patients treated with TAM was significantly improved compared with those with no TAM in ER + /HER2− postmenopausal breast cancer when TIL-low group (< 10%) was considered (HR 0.49, 95% CI 0.31–0.78, p = 0.002). But no significant benefit was obtained from TAM among patients with TIL-high group (≥ 10%) [ 12 ]. These data support the hypothesis that the inferior efficacy of ET in the TIL-high group of the ER + /HER2− subtype results in a poor prognosis.…”

Section: Introductionmentioning

confidence: 99%

An increase in tumor-infiltrating lymphocytes after treatment is significantly associated with a poor response to neoadjuvant endocrine therapy for estrogen receptor-positive/HER2-negative breast cancers

Fukui¹,

Watanabe²,

Fujimoto³

et al. 2023

Breast Cancer

View full text Add to dashboard Cite

Background The reason for the poor prognosis of estrogen receptor (ER) + /human epidermal growth factor receptor 2 (HER2)− breast cancer patients with high levels of tumor-infiltrating lymphocytes (TILs) is poorly understood. The association between TILs and response to neoadjuvant endocrine therapy (NET) was examined. Methods We recruited 170 patients with ER + /HER2− breast cancer who were treated with preoperative endocrine monotherapy. TILs were evaluated before and after NET, and their changes were noted. Furthermore, T cell subtypes were examined using CD8 and FOXP3 immunohistochemical analyses. Neutrophil and lymphocyte counts in the peripheral blood were analyzed with reference to TIL levels or changes. Responders were defined as Ki67 expression levels ≤ 2.7% after treatment. Results Post-treatment (p = 0.016), but not pre-treatment (p = 0.464), TIL levels were significantly associated with the response to NET. TIL levels increased significantly after treatment among non-responders (p = 0.001). FOXP3 + T cell counts increased significantly after treatment in patients with increased TILs (p = 0.035), but not in those without increased TILs (p = 0.281). Neutrophil counts decreased significantly after treatment in patients without increased TILs (p = 0.026), but not in patients with increased TILs (p = 0.312). Conclusion An increase in TILs after NET was significantly associated with a poor response to NET. Given that FOXP3 + T-cell counts increased, and neutrophil counts did not decrease in patients with increased TILs after NET, the induction of an immunosuppressive microenvironment was speculated to play a role in the inferior efficacy. These data might partially indicate the involvement of the immune response in the efficacy of endocrine therapy.

show abstract

“…CD19(+) B cells are identi ed as a signi cant factor in immune evasion from breast cancer due to their high tumor grade, ER-negative status, and expression of IL-10 and PD-L1. Despite this, CD19-positive B cells have been observed to inhibit the aggressiveness of triple-negative breast cancer (TNBC) and the HER2-positive BC subtype, extend patients' lifespans, and reinforce antitumor immunity (Pousette et al 2022). Additionally, other studies have demonstrated that CD19(+) B cells prolong the life of those with muscle-invasive bladder cancer (Jiang et al 2019).…”

Section: Introductionmentioning

confidence: 99%

The pan-cancer analysis uncovers the prognostic and immunotherapeutic significance of CD19 as an immune marker in tumor

Wei

Meng

Xiang

et al. 2023

Preprint

View full text Add to dashboard Cite

The specific cytotoxic effects of anti-CD19 chimeric antigen receptor (CAR) T-cell therapy have led to impressive outcomes in individuals previously treated for B-cell malignancies. However, the specific biological role of CD19(+) target cells, which exert antitumor immunity against some solid tumors, remains to be elucidated. We collected information regarding the level of CD19 mRNA and protein expression from various databases including The Cancer Genome Atlas (TCGA), Tumor Immune Estimation Resource (TIMER), GTEx, and Human Protein Atlas (HPA) for both tumor and normal samples. To evaluate the patients' prognosis according to CD19 expression, a Kaplan-Meier (KM) analysis and univariate Cox regression were performed. Furthermore, using the Estimation of Stromal and Immune Cells in Malignant Tumor Tissues Using the Expression Data (ESTIMATE) algorithm, we estimated the ratio of immune cells infiltrating malignant tumor tissues. Afterward, the GSCALite repository was employed to evaluate the vulnerability of tumors expressing CD19 to drugs used in chemotherapy. To validate the results in clinical samples of certain cancer types, immunohistochemistry was then performed. Most tumor types exhibited CD19 expression differently, apart from colon adenocarcinoma (COAD). The early diagnostic value of CD19 has been demonstrated in 9 different tumor types, and the overexpression of CD19 has the potential to extend the survival duration of patients. Multiple tumors showed a positive correlation between CD19 expression and tumor mutation burden (TMB), microsatellite instability (MSI), ESTIMATE score, immunoscore, and stromal score. Furthermore, a direct association was discovered between the expression of CD19 and the infiltration of immune cells, particularly in cases of breast invasive carcinoma (BRCA). Moreover, CD19 is highly sensitive to a variety of chemotherapy drugs. The study reveals the potential of CD19 as both a predictive biomarker and a target for different cancer immunotherapies.

show abstract

Prognostic and Predictive Significance of Stromal Tumor-Infiltrating Lymphocytes (sTILs) in ER-Positive/HER2−Negative Postmenopausal Breast Cancer Patients

Cited by 3 publications

References 55 publications

The Pan-Cancer Analysis Uncovers the Prognostic and Immunotherapeutic Significance of CD19 as an Immune Marker in Tumor

The Pan-Cancer Analysis Uncovers the Prognostic and Immunotherapeutic Significance of CD19 as an Immune Marker in Tumor

An increase in tumor-infiltrating lymphocytes after treatment is significantly associated with a poor response to neoadjuvant endocrine therapy for estrogen receptor-positive/HER2-negative breast cancers

The pan-cancer analysis uncovers the prognostic and immunotherapeutic significance of CD19 as an immune marker in tumor

Contact Info

Product

Resources

About