The immune system and response to HER2-targeted treatment in breast cancer

HER2 signaling regulates the tumor immune microenvironment and trastuzumab efficacy

“…Experimental protocols used for animal studies were approved by the Ethics Committee for Animal Experimentation of Fondazione IRCCS-INT in accordance with institutional guidelines. FVB mice were injected into the mammary fat pad with 1 × 10 6 MI6 cells, a murine mammary breast carcinoma cell line derived from transgenic mice overexpressing the human d16HER2 isoform. 15 When tumors were palpable, mice were randomized into two groups to receive three weekly i.p.…”

“…3 Recently, analyses of gene expression profiles of tumor blocks from patients enrolled in clinical trials support a relationship between tumor dependence on HER2 signaling (HER2-E by PAM50) and trastuzumab sensitivity. 4,5 Moreover, based on increasing evidence of the role of both innate and adaptive immunity in trastuzumab mechanism of action, 6,7 immune-related information such as tumor infiltrating lymphocyte count or immune-related signatures were explored and found to be predictive of trastuzumab benefit in several studies. 8 In this context, through transcriptome profiling of archival formalin-fixed paraffin embedded (FFPE) tumor blocks from HER2+ cases treated with adjuvant trastuzumab in our Institute during routine clinical practice, 9 we identified BCs exquisitely sensitive to treatment as those with both tumor dependence on HER2 signaling by PAM50 classification, as well as enriched in immune genes, 9 supporting the predictive power of both addiction to HER2 signaling and immune infiltration because of their ability to identify the same tumors.…”

DNA methylation–based immune response signature improves patient diagnosis in multiple cancers

“…In particular, tumor-infiltrating lymphocytes (TILs) have been shown to provide prognostic and predictive information. High numbers of TILs have been associated with increased survival and response rates to preoperative chemotherapy in triple-negative (TN) (2)(3)(4)(5) as well as human EGFR 2-positive (HER2) BCs treated with chemotherapy and trastuzumab (2,(4)(5)(6). Among TILs, T cell subsets are most abundant (7) and are associated with clinical outcomes (8)(9)(10)(11)) that suggest they play a major role in the antitumor immune response.…”

Diverse biology of breast cancer: search for adequate treatment

“…Это означает, что зна-чительное число пациентов с HER2-позитивной опухолью (по ИГХ) не чувствительны к одной таргетной терапии без сопровождающей цитотоксической химиотерапии такса-нами, антрациклинами и/или платиной. Гетерогенность ответа на HER2 -таргетную терапию свя-зывается с биологическим подтипом, гормонально-рецеп-торным статусом, изменениями в сигнальных патогене-тических путях, таких как фосфатидилинозитол 3-киназа (РI3К), а также с противоопухолевыми иммунными отве-тами [24,25]. Геномный анализ HER2 позитивных опухолей (по ИГХ) с оценкой профилей генной экспрессии выявил шесть подтипов РМЖ: базально-подобный, люминальный А, лю-минальный В, НЕR2-обогащенный [HER2E], низкоклауди-новый и нормально-подобный [26].…”