We are analyzing https://link.springer.com/article/10.1007/s12282-025-01707-5.

Title:
Why combine and why neoadjuvant? Tumor immunological perspectives on chemoimmunotherapy in triple-negative breast cancer | Breast Cancer
Description:
Triple-negative breast cancer (TNBC) is an aggressive subtype characterized by limited targeted therapies and high recurrence rates. While immune checkpoint inhibitors (ICIs) have shown promise, their efficacy as monotherapy is limited. Clinically, ICIs demonstrate significant benefit primarily when combined with chemotherapy, particularly in the neoadjuvant setting for early-stage TNBC, which yields superior outcomes compared to adjuvant therapy. This review elucidates the tumor immunological principles underlying these observations. We discussed how the suppressive tumor microenvironment (TME), progressive T cell exhaustion, and associated epigenetic scarring constrain ICI monotherapy effectiveness. Crucially, we highlight the immunological advantages of the neoadjuvant approach: the presence of the primary tumor provides abundant antigens, and intact tumor-draining lymph nodes (TDLNs) act as critical sites for ICI-mediated priming and expansion of naïve and precursor exhausted T cells. This robust activation within TDLNs enhances systemic anti-tumor immunity and expands the T cell repertoire, a process less effectively achieved in the adjuvant setting after tumor resection. These mechanisms provide a strong rationale for the improved pathological complete response (pCR) rates and event-free survival observed with neoadjuvant chemoimmunotherapy, as demonstrated in trials like KEYNOTE-522. We further explore the implications for adjuvant therapy decisions based on treatment response, the challenges of ICI resistance, the need for predictive biomarkers, management of immune-related adverse events (irAEs), and future therapeutic directions. Understanding the dynamic interplay between chemotherapy, ICIs, T cells, and the TME, particularly the role of TDLNs in the neoadjuvant context, is essential for optimizing immunotherapy strategies and improving outcomes for patients with TNBC.
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Keywords {🔍}

pubmed, cancer, cells, article, cell, google, scholar, immune, tumor, breast, cas, immunotherapy, tnbc, central, neoadjuvant, adjuvant, triplenegative, pembrolizumab, icis, therapy, patients, chemotherapy, treatment, checkpoint, ici, pcr, epigenetic, activation, pdl, tme, exhausted, antitumor, response, keynote, resistance, function, exhaustion, responses, inhibitors, lymph, therapeutic, expression, trial, clinical, oncol, antigen, atezolizumab, httpsdoiorgs, med, immunological,

Topics {✒️}

high-resolution spatial transcriptomics triple-negative breast cancer pd-l1-positive metastatic tnbc pre-treatment pd-l1 expression pd-1/pd-l1-checkpoint restrains triple-negative breast cancers tumor-draining lymph nodes key regulator fine-tuning article download pdf immune-related adverse events reactivates pre-existing tex pd-l1/ici effect association anti-pd cancer immunotherapy long-term immune benefit anti-tumor effector activity myeloid-derived suppressor cell b-cell/cll lymphoma 6 cell clonality/richness predicted including biomarker-driven immunotherapy anti-tumor immune responses cell anti-tumor activity anti-pd-1 checkpoint blockade repressing immune-related genes suggests long-term benefits prolonged event-free survival pd-l1-positive tnbc extending progression-free survival cell-dependent antitumor activity open access license atac-seq analysis demonstrated kazuhiro kakimi wrote high-risk early tnbc suggesting tumor-infiltrating lymphocyte full functional recovery higher pd-l1 expression pd-l1+ immunoregulatory dcs early breast cancer aggressive breast cancer pd-l1 blockade combinations event-free survival observed ici introduction breast cancer control breast cancer microenvironment distinct tme effects stem cell-related genes nab-paclitaxel reportedly exerts immune-suppressive tme state tomoharu sugie composed breast cancer immunotherapy immune cell composition

Questions {❓}

Immunotherapy in Early-Stage Triple-Negative Breast Cancer: Where Are We Now and Where Are We Headed?
What is cancer immunotherapy?
Why combine and why neoadjuvant?
Why combine and why neoadjuvant?

Schema {🗺️}

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         headline:Why combine and why neoadjuvant? Tumor immunological perspectives on chemoimmunotherapy in triple-negative breast cancer
         description:Triple-negative breast cancer (TNBC) is an aggressive subtype characterized by limited targeted therapies and high recurrence rates. While immune checkpoint inhibitors (ICIs) have shown promise, their efficacy as monotherapy is limited. Clinically, ICIs demonstrate significant benefit primarily when combined with chemotherapy, particularly in the neoadjuvant setting for early-stage TNBC, which yields superior outcomes compared to adjuvant therapy. This review elucidates the tumor immunological principles underlying these observations. We discussed how the suppressive tumor microenvironment (TME), progressive T cell exhaustion, and associated epigenetic scarring constrain ICI monotherapy effectiveness. Crucially, we highlight the immunological advantages of the neoadjuvant approach: the presence of the primary tumor provides abundant antigens, and intact tumor-draining lymph nodes (TDLNs) act as critical sites for ICI-mediated priming and expansion of naïve and precursor exhausted T cells. This robust activation within TDLNs enhances systemic anti-tumor immunity and expands the T cell repertoire, a process less effectively achieved in the adjuvant setting after tumor resection. These mechanisms provide a strong rationale for the improved pathological complete response (pCR) rates and event-free survival observed with neoadjuvant chemoimmunotherapy, as demonstrated in trials like KEYNOTE-522. We further explore the implications for adjuvant therapy decisions based on treatment response, the challenges of ICI resistance, the need for predictive biomarkers, management of immune-related adverse events (irAEs), and future therapeutic directions. Understanding the dynamic interplay between chemotherapy, ICIs, T cells, and the TME, particularly the role of TDLNs in the neoadjuvant context, is essential for optimizing immunotherapy strategies and improving outcomes for patients with TNBC.
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      headline:Why combine and why neoadjuvant? Tumor immunological perspectives on chemoimmunotherapy in triple-negative breast cancer
      description:Triple-negative breast cancer (TNBC) is an aggressive subtype characterized by limited targeted therapies and high recurrence rates. While immune checkpoint inhibitors (ICIs) have shown promise, their efficacy as monotherapy is limited. Clinically, ICIs demonstrate significant benefit primarily when combined with chemotherapy, particularly in the neoadjuvant setting for early-stage TNBC, which yields superior outcomes compared to adjuvant therapy. This review elucidates the tumor immunological principles underlying these observations. We discussed how the suppressive tumor microenvironment (TME), progressive T cell exhaustion, and associated epigenetic scarring constrain ICI monotherapy effectiveness. Crucially, we highlight the immunological advantages of the neoadjuvant approach: the presence of the primary tumor provides abundant antigens, and intact tumor-draining lymph nodes (TDLNs) act as critical sites for ICI-mediated priming and expansion of naïve and precursor exhausted T cells. This robust activation within TDLNs enhances systemic anti-tumor immunity and expands the T cell repertoire, a process less effectively achieved in the adjuvant setting after tumor resection. These mechanisms provide a strong rationale for the improved pathological complete response (pCR) rates and event-free survival observed with neoadjuvant chemoimmunotherapy, as demonstrated in trials like KEYNOTE-522. We further explore the implications for adjuvant therapy decisions based on treatment response, the challenges of ICI resistance, the need for predictive biomarkers, management of immune-related adverse events (irAEs), and future therapeutic directions. Understanding the dynamic interplay between chemotherapy, ICIs, T cells, and the TME, particularly the role of TDLNs in the neoadjuvant context, is essential for optimizing immunotherapy strategies and improving outcomes for patients with TNBC.
      datePublished:2025-05-06T00:00:00Z
      dateModified:2025-05-06T00:00:00Z
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         Immune checkpoint inhibitors (ICIs)
         Tumor microenvironment (TME)
         T cell exhaustion
         Epigenetic scar
         Neoadjuvant and adjuvant immunotherapy
         Surgical Oncology
         Oncology
         Surgery
         Cancer Research
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      name:Chemotherapy Center, Kansai Medical University Kori Hospital, Neyagawa, Osaka, Japan
      name:Chemotherapy Center, Kansai Medical University Kori Hospital, Neyagawa, Osaka, Japan

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