PURPOSE Preclinical data suggest a contribution of the immune system to chemotherapy response. In this study, we investigated the prespecified hypothesis that the presence of a lymphocytic infiltrate in cancer tissue predicts the response to neoadjuvant chemotherapy. METHODS We investigated intratumoral and stromal lymphocytes in a total of 1,058 pretherapeutic breast cancer core biopsies from two neoadjuvant anthracycline/taxane-based studies (GeparDuo, n = 218, training cohort; and GeparTrio, n = 840, validation cohort). Molecular parameters of lymphocyte recruitment and activation were evaluated by kinetic polymerase chain reaction in 134 formalin-fixed, paraffin-embedded tumor samples. Results In a multivariate regression analysis including all known predictive clinicopathologic factors, the percentage of intratumoral lymphocytes was a significant independent parameter for pathologic complete response (pCR) in both cohorts (training cohort: P = .012; validation cohort: P = .001). Lymphocyte-predominant breast cancer responded, with pCR rates of 42% (training cohort) and 40% (validation cohort). In contrast, those tumors without any infiltrating lymphocytes had pCR rates of 3% (training cohort) and 7% (validation cohort). The expression of inflammatory marker genes and proteins was linked to the histopathologic infiltrate, and logistic regression showed a significant association of the T-cell-related markers CD3D and CXCL9 with pCR. CONCLUSION The presence of tumor-associated lymphocytes in breast cancer is a new independent predictor of response to anthracycline/taxane neoadjuvant chemotherapy and provides useful information for oncologists to identify a subgroup of patients with a high benefit from this type of chemotherapy.

Tumor-Associated Lymphocytes As an Independent Predictor of Response to Neoadjuvant Chemotherapy in Breast Cancer

The systemic inflammation-based Glasgow Prognostic Score: a decade of experience in patients with cancer.

Several recent studies have identified nuclear factor-κB as a key modulator in driving inflammation to cancers. Besides this transcription factor, essential in regulating inflammation and cancer development, an inflammatory microenvironment inhabiting various inflammatory cells and a network of signaling molecules are also indispensable for the malignant progression of transformed cells, which is attributed to the mutagenic predisposition of persistent infection-fighting agents at sites of chronic inflammation. As a subverted host response to inflammation-induced tumors, the inflammatory cells and regulators may facilitate angiogenesis and promote the growth, invasion, and metastasis of tumor cells. Thus far, research regarding inflammation-associated cancer development has focused on cytokines and chemokines as well as their downstream targets in linking inflammation and cancer. Moreover, other proteins with extensive roles in inflammation and cancer, such as signal transducers and activators of transcription, Nrf2, and nuclear factor of activated T cells, are also proposed to be promising targets for future studies. The elucidation of their specific effects and interactions will accelerate the development of novel therapeutic interventions against cancer development triggered by inflammation. (Mol Cancer Res 2006;4(4):221–33)

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Inflammation, a key event in cancer development.

Background and Objectives

Simple methods to identify colorectal cancer patients at risk of recurrence are needed. This study aimed to determine if neutrophil-to-lymphocyte ratio (NLR) predicts survival in colorectal cancer patients.



Methods

Two-hundred thirty patients diagnosed with colorectal cancer over a two-year period were identified from a prospectively maintained colorectal cancer database. NLR was calculated from pre-operative full blood counts. In the case of patients who did not undergo surgery, the full blood count from their out-patient visit was used. Known prognostic factors were recorded. Overall and cancer-specific survival were calculated.



Results

Pre-operative NLR greater than 5 correlated with overall and cancer-specific survival in univariate analyses. NLR was not independent of Dukes stage.



Conclusions

Pre-operative NLR may represent a simple method of identifying colorectal cancer patients with a poor prognosis pre-operatively. J. Surg. Oncol. 2005;91:181–184. © 2005 Wiley-Liss, Inc.

Neutrophil-lymphocyte ratio as a prognostic factor in colorectal cancer.

Disease progression in cancer is dependent on the complex interaction between the tumor and the host inflammatory response. There is substantial evidence in advanced cancer that host factors, such as weight loss, poor performance status and the host systemic inflammatory response, are linked, and the latter is an important tumor-stage-independent predictor of outcome. Indeed, the systemic inflammatory response, as evidenced by an elevated level of C-reactive protein, is now included in the definition of cancer cachexia. This review examines the role of the systemic inflammatory response in predicting survival in patients with primary operable cancer. Approximately 80 studies have evaluated the role of the systemic inflammatory response using biochemical or hematological markers, such as elevated C-reactive protein levels, hypoalbuminemia or increased white cell, neutrophil and platelet counts. Combinations of such factors have been used to derive simple inflammation-based prognostic scores, such as the Gl...

Role of systemic inflammatory response in predicting survival in patients with primary operable cancer

Background:

Some studies have shown that the presence of a systemic inflammatory response, as evidenced by raised circulating concentrations of C-reactive protein (CRP), predicted recurrence and overall survival in patients with colorectal cancer. The aim of this study was to examine the relationship between the inflammatory response and overall and cancer-specific survival in patients undergoing potentially curative resection for colorectal cancer.



Methods:

A total of 174 patients considered to have undergone curative resection were studied. Circulating CRP concentrations were measured before and/or after operation.



Results:

The majority of patients were aged 65 years or more, had colonic tumours and Dukes' stage B lesions. During follow-up, 47 patients (27 per cent) developed recurrence and 59 (34 per cent) died. On univariate analysis, age (P < 0·01), Dukes' stage (P < 0·001), and CRP levels before (P < 0·01) and after (P < 0·01) operation were significantly associated with overall and cancer-specific survival. On multivariate analysis of patients in whom preoperative CRP concentration was measured, age (P < 0·01), Dukes' stage (P < 0·05) and CRP concentration (P < 0·01) were independently associated with both overall and cancer-specific survival.



Conclusion:

In patients who have undergone potentially curative resection for colorectal cancer, the presence of a systemic inflammatory response predicts a poor outcome. Copyright © 2003 British Journal of Surgery Society Ltd. Published by John Wiley & Sons Ltd

Systemic inflammatory response predicts survival following curative resection of colorectal cancer.

There is increasing evidence that both local and systemic inflammatory responses play an important role in the progression of a variety of common solid tumours. The aim of the present study was to examine the relationship between tumour T-lymphocyte subset infiltration, the systemic inflammatory response and cancer-specific survival in patients with colorectal cancer. In all, 147 patients undergoing potentially curative resection for colorectal cancer were studied. Circulating concentrations of C-reactive protein were measured prior to surgery. CD4+ and CD8+ T-lymphocyte infiltration of the tumour was assessed using immunohistochemistry and a point counting technique. When patients were grouped according to the percentage tumour volume of CD4+ T-lymphocytes, there was no difference in terms of age, sex, tumour site, stage and tumour characteristics. However, there was an inverse relationship between percentage tumour CD4+ T-lymphocytes and C-reactive protein (P<0.01). On univariate analysis, both C-reactive protein concentrations (P<0.001) and percentage tumour volume of CD4+ (P<0.05) T-lymphocytes were associated with cancer-specific survival. The results of the present study show that low tumour CD4+ T-lymphocyte infiltration is associated with elevated C-reactive protein concentrations and both predict poor cancer-specific survival.

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The relationship between tumour T-lymphocyte infiltration, the systemic inflammatory response and survival in patients undergoing curative resection for colorectal cancer.

The present study examined the relationship between tumour stage, grade, T-lymphocyte subset infiltration and survival in patients who had undergone potentially curative surgery for renal clear-cell cancer (n=73). Intratumoural CD4+ T-lymphocyte infiltrate was associated with poor cancer-specific survival, independent of grade, in this cohort.

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The relationship between T-lymphocyte infiltration, stage, tumour grade and survival in patients undergoing curative surgery for renal cell cancer.

The relationship between tumour stage, T-lymphocyte subset infiltration and survival was examined in patients with prostate cancer (n=80). On multivariate analysis PSA (HR 2.47, 95% CI 1.27–4.83, P=0.008) and CD4+ T-lymphocyte count (HR 2.29, 95% CI 1.25–4.22, P=0.008) had independent significance. Increased CD4+ T-lymphocyte infiltration within the tumour was stage independent and associated with poor outcome in patients with prostate cancer.

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The relationship between T-lymphocyte subset infiltration and survival in patients with prostate cancer

The value of combining Dukes' stage and C-reactive protein to form a cumulative prognostic score was assessed in 147 patients undergoing potentially curative resection for colorectal cancer. The cancer-specific survival rates at 3 years for patients with a cumulative prognostic score of 0, 1 and 2 were 100, 77 and 40%, respectively (HR 4.76, 2.78–8.15, P<0.001).

Evaluation of a cumulative prognostic score based on the systemic inflammatory response in patients undergoing potentially curative surgery for colorectal cancer

K. Canna

Papers

Systemic inflammatory response predicts survival following curative resection of colorectal cancer.

The relationship between tumour T-lymphocyte infiltration, the systemic inflammatory response and survival in patients undergoing curative resection for colorectal cancer.

The relationship between T-lymphocyte infiltration, stage, tumour grade and survival in patients undergoing curative surgery for renal cell cancer.

The relationship between T-lymphocyte subset infiltration and survival in patients with prostate cancer

Evaluation of a cumulative prognostic score based on the systemic inflammatory response in patients undergoing potentially curative surgery for colorectal cancer