Tumors with high-density tumor infiltrating lymphocytes constitute a favorable entity in breast cancer: a pooled analysis of four prospective adjuvant trials

Kotoula, Vassiliki; Chatzopoulos, Kyriakos; Lakis, Sotiris; Alexopoulou, Zoi; Timotheadou, Eleni; Zagouri, Flora; Pentheroudakis, George; Gogas, Helen; Galani, Eleni; Efstratiou, Ioannis; Zaramboukas, Thomas; Koutras, Angelos; Aravantinos, G.; Samantas, Epaminontas; Psyrri, Amanda; Kourea, Helen P.; Bobos, Mattheos; Papakostas, Pavlos; Kosmidis, P.; Pectasides, Dimitrios; Fountzilas, George

doi:10.18632/oncotarget.6231

Cited by 58 publications

(51 citation statements)

References 29 publications

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“…Although in a small cohort of oral cavity carcinoma patients, the number of CD4 or CD8 T-cells was not associated with overall survival [10], a recent larger retrospective study with 278 patients showed that increased CD4 and CD8 TIL levels were significant independent prognostic variables associated with favorable overall survival and recurrence-free survival [11]. A comprehensive meta-analysis of the prognostic value of the number of TILs for HNSCC patients has not been published; but meta-analyses for patients with lung cancer and breast cancer showed that high TIL numbers were independently associated with a favorable outcome in both cancer types [12, 13]. Notably, HPV-driven HNSCC has a distinct clinical response profile to chemoradiation therapy.…”

Section: Does the Number Of T-cells In The Tumor Microenvironment Matmentioning

confidence: 99%

Telltale tumor infiltrating lymphocytes (TIL) in oral, head & neck cancer

et al. 2016

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Evidence gleaned from recent studies on the role of tumor-infiltrating lymphocytes (TILs) suggests that cancer is not only a genetic disease but also an immunologic disease. Head and Neck Squamous Cell Carcinoma (HNSCC) has been a significant model to study cancer cell-immune cell interactions. First, immune cell infiltration is an important feature of these tumors. Second, HNSCC frequently develops resistance to immunogenic cytotoxicity, which provides a window to decipher how tumors engage the immune system to establish immune tolerance. Finally, chemoradiation therapy, as a central modality for HNSCC treatment, has been shown to elicit immune activation. The presence of effector immune cells in the tumor microenvironment is often associated with superior clinical response to adjuvant therapy. On the other hand, an activated immune system, in addition to limiting tumor initiation and progression, could also exert selective pressure to promote the growth of less immunogenic tumors, as a pivotal immunoediting process. But it remains unclear how cancer cell signaling regulates tumor immunogenicity and how to mitigate HNSCC-potentiated TIL suppression. In this review, we will revisit the prognostic role of TILs in HNSCC, and collectively discuss how cancer cell machinery impacts upon the plasticity of TILs.

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Section: Does the Number Of T-cells In The Tumor Microenvironment Matmentioning

confidence: 99%

Telltale tumor infiltrating lymphocytes (TIL) in oral, head & neck cancer

et al. 2016

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“…TILs are more frequent in the aggressive subtypes of breast cancer. In a pooled analysis of 4 prospective adjuvant trials [18], high levels of TILs were significantly more frequent in hormone receptor-negative tumors. In the adjuvant BIG 02-98 trial, the median percentage of TILs was the highest in estrogen receptor (ER)-negative and HER2-negative tumors [19].…”

Section: Tumor-infiltrating Lymphocytesmentioning

confidence: 99%

Tumor-Infiltrating Lymphocytes: A Promising Biomarker in Breast Cancer

Loibl

Denkert

2016

Breast Care

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There is clear evidence that the immune system plays an essential role in tumor defense. By determining tumor-infiltrating lymphocytes (TILs), the individual immunological response becomes more apparent and measurable. In breast cancer, high levels of TILs are associated with a more favorable clinical course. In this review, we describe how TILs are determined with emphasis on daily routine diagnostics. We further discuss their impact as a prognostic and predictive biomarker in the neoadjuvant and adjuvant therapy setting as well as in residual disease. We also discuss their potential future implications on further stratifying prognostic subgroups of breast cancer, thereby possibly influencing future therapy considerations.

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“…Multiple reasons may integrate for this apparently contrasting finding. For example, the double-negatives and double-positives were highly represented among tumors with high TILs that are favorable prognosticators in TNBC (61,62), double negatives may represent genomically stable TNBC that carry a better prognosis (63), while our finding on the eitherpositive phenotype may be related to the observed worse outcome observed in patients with tumors that are p53 protein positive but do not express CK5/6 and the androgen receptor (64). Plausibly, beyond these speculations, the obtained EGFR/p53 IHC profiles should be addressed as surrogate markers integrating different genomic/molecular alterations in TNBC that need further evaluation for their prognostic value in the clinical setting.…”

Section: Discussionmentioning

confidence: 99%