Table 3.
Carcinomas in which studies have found a mixed, weak or negative association between tumor-infiltrating immune cells and prognosis
| Reference | Principal findings Correlation with better prognosis |
n | P value | Stage of carcinoma | Methods | Definition of immune cells | Follow-up period (years) |
|---|---|---|---|---|---|---|---|
| Lung carcinomas | |||||||
| 46 | Positive correlation for T-cells and B-cells in squamous cell carcinoma. |
1290 | <0.05 | I-III | H, IHC | CD3+, CD4+, CD8+, and CD20+ cells in cancer cell nests. |
>10 |
| 47 | Positive correlation for CD4+ and CD8+ T-cells in NSCLC. | 109 | <0.01 | I-III | H, IHC | CD4+ and CD8+ T-cells in cancer cell nests and stroma. | >7 |
| 48 | Positive correlation for macrophages and CD8+ T-cells in NSCLC. | 199 | <0.001 | IV | H, IHC | CD8+, CD68+, c-kit+ cells in cancer cell nests and stroma. |
>5 |
| 49 | No correlation with prognosis in NSCLC. | 128 | − | I-IV | H, IHC | CD8+ T-cells in cancer cell nests, invasive margin, or cancer stroma. |
>5 |
| Breast carcinoma | |||||||
| 50 | Positive correlation for lymphoid infiltration in patients <40 years of age. |
1919 | <0.001 | I-III | H, LM | Tumor infiltrating lymphocytes. | >14 |
| 51 | Positive or negative correlation depending on estrogen receptor status. |
155 | <0.001 | I-IV | H, TMA | Lymphocyte marker genes CCL5, CD19, CD37, CD3D, CD3E, CD3G, CD3Z, CD79A, CD79B, CD8A, CD8B1, IGHG3, IGJ, IGLC1, CD14, LCK, LTB and MS4A1. |
>20 |
| 52 | No correlation with prognosis. | 75 | <0.05 | I-IV | H, IHC | Tumor infiltrating CD3+ T-cells. | − |
| 53 | Negative correlation for T-regs. | 237 | <0.05 | I-III | TMA, IHC | FoxP3+ lymphocytes in invasive tumor. | 11 |
| 54 | Negative correlation for FoxP3+ cells. | 1445 | <0.05 | I-III | TMA, IHC | FoxP3+ cells in tumor cell nests and stroma. | 11 |
| Prostate carcinoma | |||||||
| 56 | Positive correlation for high numbers of tumor infiltrating lymphocytes. |
325 | <0.05 | I-IV | H, LM | Tumor infiltrating lymphocytes. | >13 |
| 57 | Negative correlation for tumor infiltrating T-cells and B-cells. | 188 | <0.05 | I-III | H, IHC, TMA | Tumor infiltrating CD4+, CD8+, and CD20+ cells. | >18 |
| 58 | Negative correlation for tumor infiltrating mast cells. | 104 | <0.01 | I-IV | H, IHC | Tumor infiltrating tryptase-positive mast cells. | 8 |
| Head and Neck carcinoma | |||||||
| 59 | Positive correlation for CD8+ and CD20+ cells in early disease, negative for inoperable disease. |
115 | <0.05 | I-IV | H, IHC, TMA | Tumor infiltrating CD3+, CD4+, CD8+, CD20+, CD68+, FoxP3+, and GrB+ cells. |
6 |
| 60 | No correlation with prognosis. | 33 | <0.05 | I-IV | H, IHC, TMA | Tumor infiltrating CD3+, CD8+, CD20+, CD68+, FoxP3+, and GrB+ cells. |
6 |
| 61 | Positive correlation for T-regs. | 84 | <0.05 | I-IV | IHC | Tumor infiltrating CD3+, CD4+, CD25+, CD69+, and FoxP3+ cells. |
2 |
| Renal cell carcinoma | |||||||
| 62 | Negative correlation for neutrophils. | 121 | <0.001 | I-IV | H, IHC | Tumor infiltrating CD8+, CD34+, CD57+, and CD66b+ cells. |
16 |
| 63 | Negative correlation for neutrophils, positive for CD57+ natural killer cells. |
85 | <0.01 | I-IV | H, IHC | Tumor infiltrating CD4+, CD8+, CD20+, CD56+, CD57+, and CD66b+ cells. |
>6 |
| 64 | Negative correlation for mononuclear cells. | 306 | <0.05 | I-IV | H, LM | Tumor infiltrating lymphocytes. | >11 |
| 65 | Negative correlation for CD8+ T-cells, positive for CD4+ T-cells. | 79 | <0.01 | I-IV | H, FACS | Tumor infiltrating CD3+, CD4+, CD8+, CD11+, CD16+, CD19+, CD20+, CD45RA+, and CD57+ cells. |
>5 |
| 66 | Negative correlation for CD4+ T-cells. | 73 | <0.001 | I-IV | H, IHC | Tumor infiltrating CD4+ and CD8+ T-cells. | >3 |
FACS: flow cytometry; H: histopathological analysis; IHC: immunohistochemistry; LM: light microscopy; TMA: tissue microarray; T-regs: regulatory T-cells; NSCLC, non-small-cell lung cancer.