Immunophenotype of lymphocytic infiltration in medullary carcinoma of the breast

Kuroda, Hajime; Tamaru, Jun‐ichi; Sakamoto, Goi; Ohnisi, Kiyoshi; Itoyama, Shinji

doi:10.1007/s00428-004-1143-9

Cited by 52 publications

(42 citation statements)

References 17 publications

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“…It has also been reported that active CD8 þ cytotoxic T lymphocytes are the principal cells attacking breast carcinoma cells. [18][19][20] In medullary carcinoma of breast, our results strongly suggest that there is an active immune response against the tumor. Tumor infiltrating lymphocytes were typically present in both the stroma and within the epithelial nests of tumor cells.…”

Section: Discussionmentioning

confidence: 89%

Tumor infiltrating lymphocytes differ in invasive micropapillary carcinoma and medullary carcinoma of breast

et al. 2008

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Tumor infiltrating lymphocytes have been correlated with a better prognosis for some tumors and medullary carcinoma of breast is a good example. However, in a recent study of invasive micropapillary carcinoma of breast, tumor infiltrating lymphocytes were associated with increased lymph node metastasis and a poorer prognosis. To explore possible mechanisms underlying this difference in immune responsiveness and tumor behavior, 28 cases of invasive micropapillary carcinoma with prominent lymphocyte infiltration were compared with 29 cases of medullary carcinoma. In both tumors, the majority of tumor infiltrating lymphocytes were T lymphocytes (Po0.01) with CD8 þ T lymphocytes predominant (Po0.01). Significantly, functional differences in CD8 þ cytotoxic T lymphocytes were identified in the two types of tumor. While lymphocytes infiltrated both the stroma and epithelial components of medullary carcinoma, the tumor infiltrating lymphocytes of invasive micropapillary carcinoma were almost exclusively confined to the stroma. Tumor infiltrating lymphocytes of medullary carcinoma showed stronger expression of FasL than those in invasive micropapillary carcinoma (Po0.01) and medullary carcinoma cells exhibited stronger expression of Fas than invasive micropapillary carcinoma cells did (Po0.01). In the subgroups of tumors with strong ( þ þ / þ þ þ ) Fas expression, double immunohistochemistry revealed that most of the tumor infiltrating lymphocytes in medullary carcinoma, particularly those infiltrating the tumor nests, were CD8 þ cytotoxic T lymphocytes, but not so in invasive micropapillary carcinoma. Furthermore, upregulated expression of perforin, granzyme B and FasL by cytotoxic T lymphocytes was greater in medullary carcinoma than invasive micropapillary carcinoma (Po0.01, respectively). The results suggest that effective immunity provided by tumor infiltrating lymphocytes varies in different tumors and the relative lack of tumor-killing cytotoxic T lymphocytes in invasive micropapillary carcinoma may explain, in part, the adverse association of tumor infiltrating lymphocytes with the biological behavior of invasive micropapillary carcinoma of breast. Modern Pathology (2008Pathology ( ) 21, 1101Pathology ( -1107 doi:10.1038/modpathol.2008 published online 9 May 2008 Keywords: tumor infiltrating lymphocytes; invasive micropapillary carcinoma; medullary carcinoma; breast; laser scanning confocal microscope Local and systemic inflammatory responses play an important role in the progression of a variety of common solid tumors. Tumor infiltrating lymphocytes are believed to represent the local immune response, a key mechanism in controlling tumor growth and metastasis, and an independent prognostic indicator for many tumors.1,2 This is well demonstrated in medullary carcinoma of breast which is characterized by large sheets of poorly differentiated tumor cells and a prominent lymphoplasmacytic infiltrate, rare lymph node metastasis and a good prognosis. 3 Invasive micropapillary carcinoma of breast is composed of sma...

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Section: Discussionmentioning

confidence: 89%

Tumor infiltrating lymphocytes differ in invasive micropapillary carcinoma and medullary carcinoma of breast

et al. 2008

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“…For example, vaccination with her2/neu peptides induces specific cellular immunity in patients with breast cancer (31)(32)(33), and HER-2/neu vaccination may offer clinical benefit particularly in the setting of minimal residual disease (32,33). These findings underscore an increasing appreciation that, beyond melanoma and renal cell carcinoma, carcinomas of the breast can be targeted by cellular immunity (24,(28)(29)(30)34).…”

Section: Discussionmentioning

confidence: 98%

Telomerase-Specific T-Cell Immunity in Breast Cancer: Effect of Vaccination on Tumor Immunosurveillance

Domchek¹,

Recio

Mick

et al. 2007

Cancer Research

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The human telomerase reverse transcriptase (hTERT) is nearly universally overexpressed in human cancer, contributes critically to oncogenesis, and is recognized by cytotoxic T cells that lyse tumors. CD8+ T cells specific for hTERT naturally occur in certain populations of cancer patients in remission, but it remains poorly understood whether such T cells could contribute to tumor immunosurveillance. To address this issue, we induced hTERT-specific T cells in vivo via peptide vaccination in 19 patients with metastatic breast cancer who otherwise had no measurable T-cell responses to hTERT at baseline. Tumor-infiltrating lymphocytes (TIL) were evident after, but not before vaccination, with 4% to 13% of postvaccine CD8+ TIL specific for the immunizing hTERT peptide. Induction of TIL manifested clinically with tumor site pain and pruritus and pathologically with alterations in the tumor microenvironment, featuring histiocytic accumulation and widespread tumor necrosis. hTERT-specific CD8+ T cells were also evident after vaccination in the peripheral blood of patients and exhibited effector functions in vitro including proliferation, IFN-; production, and tumor lysis. An exploratory landmark analysis revealed that median overall survival was significantly longer in those patients who achieved an immune response to hTERT peptide compared with patients who did not. Immune response to a control cytomegalovirus peptide in the vaccine did not correlate with survival. These results suggest that hTERT-specific T cells could contribute to the immunosurveillance of breast cancer and suggest novel opportunities for both therapeutic and prophylactic vaccine strategies for cancer. [Cancer Res 2007;67(21):10546-55]

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“…An association of GrB þ B cells with solid tumors has not been reported so far. However, while infiltration of certain tumors with B cells can be associated with a good prognosis (27)(28)(29)(30), in others the presence of B cells support a tumor-protective environment (31)(32)(33). We therefore hypothesized that GrB-expressing B cells may phenotypically represent Breg and may be present in the microenvironment of human tumors.…”

Section: Introductionmentioning

confidence: 99%

Interleukin 21–Induced Granzyme B–Expressing B Cells Infiltrate Tumors and Regulate T Cells

et al. 2013

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The pathogenic impact of tumor-infiltrating B cells is unresolved at present, however, some studies suggest that they may have immune regulatory potential. Here, we report that the microenvironment of various solid tumors includes B cells that express granzyme B (GrB, GZMB), where these B cells can be found adjacent to interleukin (IL)-21-secreting regulatory T cells (Treg) that contribute to immune tolerance of tumor antigens. Because Tregs and plasmacytoid dendritic cells are known to modulate T-effector cells by a GrB-dependent mechanism, we hypothesized that a similar process may operate to modulate regulatory B cells (Breg). IL-21 induced outgrowth of B cells expressing high levels of GrB, which thereby limited T-cell proliferation by a GrB-dependent degradation of the T-cell receptor z-chain. Mechanistic investigations into how IL-21 induced GrB expression in B cells to confer Breg function revealed a CD19

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Immunophenotype of lymphocytic infiltration in medullary carcinoma of the breast

Cited by 52 publications

References 17 publications

Tumor infiltrating lymphocytes differ in invasive micropapillary carcinoma and medullary carcinoma of breast

Tumor infiltrating lymphocytes differ in invasive micropapillary carcinoma and medullary carcinoma of breast

Telomerase-Specific T-Cell Immunity in Breast Cancer: Effect of Vaccination on Tumor Immunosurveillance

Interleukin 21–Induced Granzyme B–Expressing B Cells Infiltrate Tumors and Regulate T Cells

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