Predictive value of improvement in the immune tumour microenvironment in patients with breast cancer treated with neoadjuvant chemotherapy

Goto, Wataru; Kashiwagi, Shinichiro; Asano, Yuka; Takada, Koji; Takahashi, Katsuyuki; Hatano, Takaharu; Takashima, Tsutomu; Tomita, Shuhei; Motomura, Hisashi; Ohsawa, Masahiko; Hirakawa, Kosei; Ohira, Masaichi

doi:10.1136/esmoopen-2017-000305

Cited by 45 publications

(35 citation statements)

References 47 publications

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“…A stable or decreasing CD8 score during treatment was also correlated with better CSS; accordingly, those with increasing CD8 levels had worse treatment response and survival. This is in conflict with results published in breast cancer that an increasing CD8 level during neoadjuvant chemotherapy or a high CD8 score thereafter correlated with good overall survival . Also, in rectal cancer, patients with high CD8 scores after CRT showed better disease‐free survival .…”

Section: Discussioncontrasting

confidence: 99%

Immunologic impact of chemoradiation in cervical cancer and how immune cell infiltration could lead toward personalized treatment

Lippens

Bockstal

Jaeghere

et al. 2020

Intl Journal of Cancer

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We investigated the potential of tumor-infiltrating immune cells (ICs) as predictive or prognostic biomarkers for cervical cancer patients. In total, 38 patients treated with (chemo)radiotherapy and subsequent surgery were included in the current study. This unique treatment schedule makes it possible to analyze IC markers in pretreatment and posttreatment tissue specimens and their changes during treatment. IC markers for T cells (CD3, CD4, CD8 and FoxP3), macrophages (CD68 and CD163) and B cells (CD20), as well as IL33 and PD-L1, were retrospectively analyzed via immunohistochemistry. Patients were grouped in the low score or high score group based on the amount of positive cells on immunohistochemistry. Correlations to pathological complete response (pCR), cause-specific survival (CSS) and metastasis development during follow-up were evaluated. In analysis of pretreatment biopsies, significantly more pCR was seen for patients with CD8 = CD3, CD8 ≥ CD4, positive IL33 tumor cell (TC) scores, IL33 IC < TC and PD-L1 TC ≥5%. Besides patients with high CD8 scores, also patients with CD8 ≥ CD4, CD163 ≥ CD68 or PD-L1 IC ≥5% had better CSS. In the analysis of posttreatment specimens, less pCR was observed for patients with high CD8 or CD163 scores. Patients with decreasing CD8 or CD163 scores between pretreatment and posttreatment samples showed more pCR, whereas those with increasing CD8 or decreasing IL33 IC scores showed a worse CSS. Meanwhile, patients with an increasing CD3 score or stable/increasing PD-L1 IC score showed more metastasis during follow-up. In this way, the intratumoral IC landscape is a promising tool for prediction of outcome and response to (chemo)radiotherapy.K.V. and H.D. contributed equally to this work Additional Supporting Information may be found in the online version of this article.

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Section: Discussioncontrasting

confidence: 99%

Immunologic impact of chemoradiation in cervical cancer and how immune cell infiltration could lead toward personalized treatment

Lippens

Bockstal

Jaeghere

et al. 2020

Intl Journal of Cancer

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“…104 The presence of FOXP3+ sTILs, instead of the intra-tumoral FOXP3+ TILs, was reported to be able to forecast a poor prognosis, and the CD8+/FOXP3+ TIL ratio (CFR) can be invented to identify well responders to NAC in breast cancers, especially in TNBC. 95,105 The increasing pCR rates and better RFS were obviously relevant to high changes of CFR in breast cancer patients with NAC, 106 especially in HR+/HER2subgroups. 107 In contrast, γδ TILs were responsible for poor prognosis in another study.…”

Section: Tumor-infiltrating Lymphocytes (Tils)mentioning

confidence: 97%

<p>Predictors of Neoadjuvant Chemotherapy Response in Breast Cancer: A Review</p>

Xu¹,

Chen²,

Deng³

et al. 2020

OTT

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Neoadjuvant chemotherapy (NAC) largely increases operative chances and improves prognosis of the local advanced breast cancer patients. However, no specific means have been invented to predict the therapy responses of patients receiving NAC. Therefore, we focus on the alterations of tumor tissue-related microenvironments such as stromal tumor-infiltrating lymphocytes status, cyclin-dependent kinase expression, noncoding RNA transcription or other small molecular changes, in order to detect potentially predicted biomarkers which reflect the therapeutic efficacy of NAC in different subtypes of breast cancer. Further, possible mechanisms are also discussed to discover feasible treatment targets. Thus, these findings will be helpful to promote the prognosis of breast cancer patients who received NAC and summarized in this review.

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“…A high level of CD8+ TILs and a high CD8/FOXP3+ TIL ratio in a residual tumour could predict an improvement in RFS and breast cancer-specific survival (BCSS) in TNBC patients with non-pCR following neoadjuvant anthracycline + taxane chemotherapy [39]. Recently, Goto et al [40] noticed an increased CD8/FOXP3+ TIL ratio following treatment with FEC100 followed by paclitaxel. This increase was significantly associated with improved clinical outcomes in TNBC and hormone-responsive breast cancer.…”

Section: Til Subsets and Neoadjuvant Response Cd3+ Tilsmentioning

confidence: 99%

The Immune Microenvironment in Breast Carcinoma: Predictive and Prognostic Role in the Neoadjuvant Setting

2019

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The immune system is responsible for the maintenance of tissue homeostasis by initiating inflammatory reactions that involve the activation of innate and adaptive immune cells.• In cancer, immune responses that aim to eliminate the tumour are elicited. However, the neoplastic cells may escape the immune control through immune-editing which depends on both tumour and immune cell interactions. • New therapies have the potential to reactivate the immune response against cancer, e.g., in melanomas and lung cancer, and this is associated with improved outcomes. Novel Insights• Immune cell subpopulations, especially tumour-infiltrating lymphocytes (TILs) in the breast carcinoma microenvironment, can influence the tumour response to various neoadjuvant chemotherapy regimens, particularly in triple-negative and HER2-positive breast cancers. • Recognition of TIL subtypes and locations in relation to tumour cells in breast carcinoma are promising for the development of more effective options of targeted therapy. • The International TILs Working Group recommends the assessment of TILs on H&E sections. StromalTILs should be analysed excluding necrotic and crushed areas. Immunohistochemical and digital assessments of TILs are currently limited to the research setting. AbstractThe prognostic value of the immune cell infiltrate in the breast carcinoma microenvironment is still uncertain. We reviewed published articles analysing the infiltration of inflammatory cells in the microenvironment of breast carcinoma. Data revealed the importance of infiltration of these immune cells in the prognosis of breast carcinoma, particularly the triple-negative and HER2-positive phenotypes. Tumourinfiltrating lymphocytes and their subtypes play a fundamental role in predicting the pathological complete response (pCR) to neoadjuvant chemotherapy. More research aiming to dissect a complex network of communication between cancer cells and other cellular components of the tumour microenvironment is necessary to develop more effective therapeutic approaches.

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Predictive value of improvement in the immune tumour microenvironment in patients with breast cancer treated with neoadjuvant chemotherapy

Cited by 45 publications

References 47 publications

Immunologic impact of chemoradiation in cervical cancer and how immune cell infiltration could lead toward personalized treatment

Immunologic impact of chemoradiation in cervical cancer and how immune cell infiltration could lead toward personalized treatment

<p>Predictors of Neoadjuvant Chemotherapy Response in Breast Cancer: A Review</p>

The Immune Microenvironment in Breast Carcinoma: Predictive and Prognostic Role in the Neoadjuvant Setting

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