TNFR2+ TILs are significantly associated with improved survival in triple-negative breast cancer patients

Dadiani, Maya; Necula, Daniela; Kahana-Edwin, Smadar; Oren, Nino; Baram, Tamir; Marin, I; Morzaev-Sulzbach, Dana; Pavlovski, Anya; Balint‐Lahat, Nora; Anafi, Liat; Wiemann, Stefan; Körner, Cindy; Gal‐Yam, Einav Nili; Avivi, Camila; Kaufman, Bella; Barshack, Iris; Ben‐Baruch, Adit

doi:10.1007/s00262-020-02549-0

Cited by 12 publications

(14 citation statements)

References 45 publications

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“…However, our recent study on TNFR2 TILs revealed much more complex roles for TNFR2 in TNBC [44]. In contrast to other cancer types, we found that TNFR2+ TILs were significantly associated with improved survival in TNBC patients [44].…”

Section: Discussioncontrasting

confidence: 58%

Section: Introductionmentioning

confidence: 93%

“…With this information in mind, in our published study, we determined the subset of TNFR2+ TILs in TNBC patient tumors [44]. Unlike studies of TNFR2+ TILs in other tumor types, our research indicated that high proportions of TNFR2+ TILs in TNBC patient biopsies were significantly associated with improved survival [44]. Here, it is important to indicate that in our study, we determined TNFR2+ TILs in patient biopsies taken prior to chemotherapy (adjuvant-treated patients); however, because survival rates are routinely determined after chemotherapy, our results may have reflected the fact that TNFR2+ TILs, which were present in the tumors prior to chemotherapy, were affected by the treatment in a manner that increased anti-tumor activities and contributed to improved survival rates in the patients.…”

Section: Introductionmentioning

confidence: 99%

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Chemotherapy Shifts the Balance in Favor of CD8+ TNFR2+ TILs in Triple-Negative Breast Tumors

Baram

Erlichman

Dadiani

et al. 2021

Cells

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Triple-negative breast cancer (TNBC) is primarily treated via chemotherapy; in parallel, efforts are made to introduce immunotherapies into TNBC treatment. CD4+ TNFR2+ lymphocytes were reported as Tregs that contribute to tumor progression. However, our published study indicated that TNFR2+ tumor-infiltrating lymphocytes (TNFR2+ TILs) were associated with improved survival in TNBC patient tumors. Based on our analyses of the contents of CD4+ and CD8+ TILs in TNBC patient tumors, in the current study, we determined the impact of chemotherapy on CD4+ and CD8+ TIL subsets in TNBC mouse tumors. We found that chemotherapy led to (1) a reduction in CD4+ TNFR2+ FOXP3+ TILs, indicating that chemotherapy decreased the content of CD4+ TNFR2+ Tregs, and (2) an elevation in CD8+ TNFR2+ and CD8+ TNFR2+ PD-1+ TILs; high levels of these two subsets were significantly associated with reduced tumor growth. In spleens of tumor-bearing mice, chemotherapy down-regulated CD4+ TNFR2+ FOXP3+ cells but the subset of CD8+ TNFR2+ PD-1+ was not present prior to chemotherapy and was not increased by the treatment. Thus, our data suggest that chemotherapy promotes the proportion of protective CD8+ TNFR2+ TILs and that, unlike other cancer types, therapeutic strategies directed against TNFR2 may be detrimental in TNBC.

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Section: Discussioncontrasting

confidence: 58%

Section: Introductionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

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Chemotherapy Shifts the Balance in Favor of CD8+ TNFR2+ TILs in Triple-Negative Breast Tumors

Baram

Erlichman

Dadiani

et al. 2021

Cells

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“…It has been verified that a greater lymphocytic infiltration in the initial biopsy predicts a higher rate of pCR after neoadjuvant therapy, thus providing a better prognosis in early TNBC regardless of the systemic treatment used and conferring an improvement of around 10% in DFS and OS due to each 10% increase in TILs. [76][77][78] Furthermore, the expression of TILs may also be a predictor of response to CT with carboplatin in neodayuvance. 79 It has been observed that patients with high expression of TILs have a similar DFS and OS regardless of whether or not they received NACT in very early stages of TNBC.…”

Section: New Strategiesmentioning

confidence: 99%

Update on systemic treatment in early triple negative breast cancer

et al. 2021

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Triple negative breast cancer (TNBC) is a heterogeneous disease representing about 15% of all breast cancers. TNBC are usually high-grade histological tumors, and are generally more aggressive and difficult to treat due to the lack of targeted therapies available, and chemotherapy remains the standard treatment. There is a close relationship between pathological complete response after chemotherapy treatment and higher rates of disease-free survival and overall survival. In this review of systemic treatment in early triple negative breast cancer, our purpose is to analyze and compare different therapies, as well as to highlight the novelties of treatment in this breast cancer subtype.

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“…Further characterization of the TILs revealed that the Treg subpopulation of T-cells in those patients resulted in an unfavorable prognosis [71]. Patients with CD8 infiltrated cells usually had a favorable prognosis [72]. The isolation of CD8 + TILs from fresh tumor tissues and infusion to the patient following the expansion of the cells, so-called the adoptive transfer of T-cells, has emerged as a promising immunotherapy modality.…”

Section: Genetically Modified T-lymphocytesmentioning

confidence: 99%

Immune gene therapy of cancer

Akbulut

2020

Turk J Med Sci

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Cancer gene therapy emerged as a promising treatment modality 3 decades ago. However, the failure of the first gene therapy trials in cancer treatment has decreased its popularity. Likewise, immunotherapy has followed a similar course. While it was a popular and promising treatment with IL-2 and interferon and cancer vaccines in the 1980s, it later lost its popularity. Immunotherapy became one of the main options for cancer treatment with the successful use of immune checkpoint inhibitors in clinics approximately 10 years ago. The success of immunotherapy has increased even more with the introduction of cancer gene therapy methods in this area. With the identification of the oncolytic herpes simplex virus and Chimeric antigen receptor (CAR) T-cells, immune gene therapy has become an essential modality in cancer treatments such as surgery, radiotherapy, chemotherapy, and targeted therapies.

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TNFR2+ TILs are significantly associated with improved survival in triple-negative breast cancer patients

Cited by 12 publications

References 45 publications

Chemotherapy Shifts the Balance in Favor of CD8+ TNFR2+ TILs in Triple-Negative Breast Tumors

Chemotherapy Shifts the Balance in Favor of CD8+ TNFR2+ TILs in Triple-Negative Breast Tumors

Update on systemic treatment in early triple negative breast cancer

Immune gene therapy of cancer

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