A Role for T-Lymphocytes in Human Breast Cancer and in Canine Mammary Tumors

Table 1

Studies of a generalized lymphocytic infiltration in human breast cancer.

Author	Year	Patients (𝑛)	Analysis	Location	Type	Comments
Aaltomaa and Lipponen [52]	1992	489	Semiquantitative; (none/mild-moderate-severe)	Peritumoral; Intratumoral	Lymphocytic infiltration	Better prognosis, positive correlation with the lack of regional lymph nodes involvement, with a smaller diameter of the tumor, with a lower histologic grade and with a larger time free of disease
Carlomagno et al. [53]	1995	1257	Semiquantitative; (absent/present)	Peritumoral	Lympho-plasmacytic infiltration	Poorer overall survival in multivariate survival analysis in particularly patients with grade I and II
Ménard et al. [54]	1997	1919	Semiquantitative; (absent/present)	Intratumoral	Lymphoid infiltration	Better overall survival in patients <40 years of age, no significant association in patients >40 in multivariate survival analysis
Marsigliante et al. [55]	1999	90	Quantitative (computerised counting)	Intratumoral	T-lymphocyte infiltration	CD3+ TILs was directly correlated to age, lymph node negative patients had tumors infiltrated by fewer CD4+ TILs with respect to lymph node positive patients
Georgiannos et al. [56]	2003	60	Semiquantitative (0 = none; 1 = rare cells; 2 = moderate numbers; and 3 = many positive cells)	Intratumoral	Lymphocytic infiltration	A significant association was found between the intensity of TIL and the number of positive nodes
Campbell et al. [25]	2005	84 patients; 26 healthy volunteers	The flow cytometry analysis was performed using CELLQuest software (BD Biosciences)	Peripheral blood and bone marrow aspirates	Peripheral blood lymphocytes	The percentages of both CD4+ and CD8+ cells were significantly lower in patients with breast cancer compared to healthy controls. A correlation was observed between number of micrometastases in the bone marrow and T cell responsiveness
Lee et al. [57]	2006	679	Semiquantitative; (none-mild-moderate-severe)	Peritumoral; Intratumoral	General inflammation infiltrate	Better recurrence-free survival and overall survival in multivariate survival analysis
Macchetti et al. [19]	2006	23	Flow cytometry quantitative analysis	Intratumoral	Lymphocytic infiltration	In the patients with lymph node metastasis, an increased mean percentage of tumor infiltrating CD4+ T-cells, but not CD8+ T-cells was observed and was correlated with worse prognosis
Al Murri et al. [58]	2008	168	Quantitative analysis	Peritumoral; Intratumoral	CD4 and CD8	No significant association
Calabrò et al. [59]	2009	155	Quantitative analysis microarray based screening for Li-associated genes		Lymphocytic infiltration	Poorer overall survival in ER+ patients and better overall survival in ER− patients
Rakha et al. [60]	2009	1597	Semiquantitative; (mild-severe)	Peritumoral; Intratumoral	General inflammation	Better recurrence-free survival and overall survival
Rody et al. [61]	2009	1263	Quantitative analysis	Peritumoral; Intratumoral	CD3	Better recurrence free survival in cases who had HER-2+
Matkowski et al. [62]	2009	88	Semiquantitative (percentage of positive stained cells: 0 = none, 1 = up to 33%, 2 = 33–66%, 3 = more than 66%; intensity of the lymphocytic infiltrate: 1-low, 2-moderate, 3-high)	Intratumoral	Lymphocytic infiltration	In early breast cancer the presence of CD8+ and CD4+ cells was correlated with lymph node involvement and unfavorable prognosis
Baker et al. [63]	2011	1953	Quantitative analysis (TMA)	Peritumoral; Intratumoral	CD8	Better cancer-specific survival in only high grade ER− tumor in multivariate survival analysis whereas poorer cancer specific survival in low grade ER+ tumor in univariate analysis
Ladoire et al. [64]	2011	162	Semiquantitative; (none-mild-moderate-severe)	Peritumoral; Intratumoral	CD8	Better recurrence-free survival after chemotherapy; CD8/FOXP3 ratio independent predictive factor associated with improved recurrence-free and overall survival after chemotherapy
Liu et al. [65]	2011	1270	Quantitative analysis	Peritumoral; Intratumoral	CD8	No significant association
Mahmoud et al. [66]	2011	1334	Quantitative analysis (TMA)	Peritumoral; Intratumoral	CD8	Better cancer-specific survival in multivariate survival analysis. Better recurrence free survival and cancer specific survival in only ER− in univariate survival analysis. Whereas no significant association in ER+
West et al. [67]	2011	255	Quantitative analysis microarray based on information in the BioGPS gene portal	Intratumoral	Lymphocytic infiltration	TIL that express cytotoxic markers was strongly associated with favorable outcome after anthracycline based treatment of ER− breast cancer patients
Ruffell et al. [68]	2012	20	Flow cytometry, immunohistochemistry, and confocal immunofluorescence quantitative analysis	Intratumoral	Leukocyte infiltration	Tumors from breast cancer patients treated with neoadjuvant chemotherapy contained an increased CD8/CD4 T-cell ratio compared with tumors removed from patients treated primarily by surgery alone