Tumor-infiltrating lymphocytes are associated with poor prognosis in invasive lobular breast carcinoma

Tille, Jean Christophe; Vieira, André Filipe; Saint-Martin, C.; Djerroudi, Lounes; Furhmann, Laëtitia; Bidard, François-Clément; Kirova, Youlia; Tardivon, A.; Reyal, Fabien; Carton, Matthieu; Vincent‐Salomon, Anne

doi:10.1038/s41379-020-0561-9

Cited by 32 publications

(48 citation statements)

References 42 publications

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“…The sTIL assessment of the matched metastases showed that the sTIL infiltration was unrelated to metastatic site [38]. In another large study, TIL content was categorised into 3 groups: no TILs (n = 239), ≤ 5% TILs (n = 185), and > 5% TILCs (n = 39 [69];), with a mean TIL score of 2.7%. Here, TILs could stratify poor outcome independently of lymph node status or molecular subtype of ILC.…”

Section: The Immune Microenvironment Of Ilcmentioning

confidence: 99%

“…The emerging field of immuno-oncology has precipitated standardisation of the assessment of tumour infiltrating lymphocytes (TILs) [67]. Long considered to be immune 'cold' (limited TILs), two recent studies [68,69] showed that TIL levels were indeed lower than those observed in IBC-NST, but nevertheless that a proportion of ILC elicit high TILs that likely impact the behaviour of the tumour. Desmedt and colleagues demonstrated high numbers of TILs (> 10%) were present in approximately 15% ILC cases (cohort contained 50% classic ILC and 50% ILC variants), and that this was associated with young age at diagnosis, positive lymph nodes, increased proliferation, and ultimately with a poorer prognosis [68].…”

Section: The Immune Microenvironment Of Ilcmentioning

confidence: 99%

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Invasive lobular carcinoma of the breast: the increasing importance of this special subtype

et al. 2021

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Invasive lobular carcinoma (ILC) is the most common of the breast cancer special types, accounting for up to 15% of all breast cancer cases. ILCs are noted for their lack of E-cadherin function, which underpins their characteristic discohesive growth pattern, with cells arranged in single file and dispersed throughout the stroma. Typically, tumours are luminal in molecular subtype, being oestrogen and progesterone receptor positive, and HER2 negative. Since last reviewing the lobular literature (McCart Reed et al., Breast Cancer Res 17:12, 2015), there has been a considerable increase in research output focused on this tumour type, including studies into the pathology and management of disease, a high-resolution definition of the genomic landscape of tumours as well as the evolution of several potential therapeutic avenues. There abounds a huge amount of new data, which we will review herein.

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Section: The Immune Microenvironment Of Ilcmentioning

confidence: 99%

Section: The Immune Microenvironment Of Ilcmentioning

confidence: 99%

Invasive lobular carcinoma of the breast: the increasing importance of this special subtype

et al. 2021

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“…Pathological complete response to neoadjuvant chemotherapy is rare and resection margins are more often positive [20,[36][37][38]. ILC differs from BC of no special type (NST, formerly known as ductal BC) with respect to DNA copy number (CN) alterations, gene expression profiles, mutational characteristics, and tumor microenvironment (immune cells and cancer-associated fibroblasts) [39][40][41][42][43][44][45][46].…”

Section: Introductionmentioning

confidence: 99%

Lobular Breast Cancer: Histomorphology and Different Concepts of a Special Spectrum of Tumors

Christgen

Floris

Marchiò

et al. 2021

Cancers

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Invasive lobular breast cancer (ILC) is the most common special histological type of breast cancer (BC). This review recapitulates developments in the histomorphologic assessment of ILC from its beginnings with the seminal work of Foote and Stewart, which was published in 1941, until today. We discuss different concepts of ILC and their implications. These concepts include (i) BC arising from mammary lobules, (ii) BC growing in dissociated cells and single files, and (iii) BC defined as a morpho-molecular spectrum of tumors with distinct histological and molecular characteristics related to impaired cell adhesion. This review also provides a comprehensive overview of ILC variants, their histomorphology, and differential diagnosis. Furthermore, this review highlights recent advances which have contributed to a better understanding of the histomorphology of ILC, such as the role of the basal lamina component laminin, the molecular specificities of triple-negative ILC, and E-cadherin to P-cadherin expression switching as the molecular determinant of tubular elements in CDH1-deficient ILC. Last but not least, we provide a detailed account of the tumor microenvironment in ILC, including tumor infiltrating lymphocyte (TIL) levels, which are comparatively low in ILC compared to other BCs, but correlate with clinical outcome. The distinct histomorphology of ILC clearly reflects a special tumor biology. In the clinic, special treatment strategies have been established for triple-negative, HER2-positive, and ER-positive BC. Treatment specialization for patients diagnosed with ILC is just in its beginnings. Accordingly, ILC deserves greater attention as a special tumor entity in BC diagnostics, patient care, and cancer research.

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“…In general, antitumor immunity is strongly reliant on the trafficking of CD8 + T cells in both primary and metastatic tumor microenvironments (TMEs) and can be characterized as a highly dynamic and tightly regulated process (8)(9)(10). There is abundant preclinical and clinical evidence that the presence of tumor-infiltrating lymphocytes (TILs) correlates with favorable clinical outcomes (11)(12)(13)(14)(15)(16)(17), but contradictory results have also been reported (18,19). Moreover, recent studies have demonstrated that the spatial distribution patterns of TILs within the tumor microenvironment may play an even more drastic role in determining the prognostic outcome, than the density of TILs alone (20)(21)(22).…”

Section: Introductionmentioning

confidence: 99%

The Cancer Cell Dissemination Machinery as an Immunosuppressive Niche: A New Obstacle Towards the Era of Cancer Immunotherapy

et al. 2021

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Although cancer immunotherapy has resulted in unpreceded survival benefits to subsets of oncology patients, accumulating evidence from preclinical animal models suggests that the immunosuppressive tumor microenvironment remains a detrimental factor limiting benefit for many patient subgroups. Recent efforts on lymphocyte-mediated immunotherapies are primarily focused on eliminating cancer foci at primary and metastatic sites, but few studies have investigated the impact of these therapies on the highly complex process of cancer cell dissemination. The metastatic cascade involves the directional streaming of invasive/migratory tumor cells toward specialized blood vessel intravasation gateways, called TMEM doorways, to the peripheral circulation. Importantly, this process occurs under the auspices of a specialized tumor microenvironment, herewith referred to as “Dissemination Trajectory”, which is supported by an ample array of tumor-associated macrophages (TAMs), skewed towards an M2-like polarization spectrum, and which is also vital for providing microenvironmental cues for cancer cell invasion, migration and stemness. Based on pre-existing evidence from preclinical animal models, this article outlines the hypothesis that dissemination trajectories do not only support the metastatic cascade, but also embody immunosuppressive niches, capable of providing transient and localized immunosubversion cues to the migratory/invasive cancer cell subpopulation while in the act of departing from a primary tumor. So long as these dissemination trajectories function as “immune deserts”, the migratory tumor cell subpopulation remains efficient in evading immunological destruction and seeding metastatic sites, despite administration of cancer immunotherapy and/or other cytotoxic treatments. A deeper understanding of the molecular and cellular composition, as well as the signaling circuitries governing the function of these dissemination trajectories will further our overall understanding on TAM-mediated immunosuppression and will be paramount for the development of new therapeutic strategies for the advancement of optimal cancer chemotherapies, immunotherapies, and targeted therapies.

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Tumor-infiltrating lymphocytes are associated with poor prognosis in invasive lobular breast carcinoma

Cited by 32 publications

References 42 publications

Invasive lobular carcinoma of the breast: the increasing importance of this special subtype

Invasive lobular carcinoma of the breast: the increasing importance of this special subtype

Lobular Breast Cancer: Histomorphology and Different Concepts of a Special Spectrum of Tumors

The Cancer Cell Dissemination Machinery as an Immunosuppressive Niche: A New Obstacle Towards the Era of Cancer Immunotherapy

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