The association between inflammation and cancer was first described years ago and has been well studied since. O’Callaghan et al [13] described the role of inflammation in the etiopathogenesis of lung cancer, and multiple studies have confirmed the prognostic value of inflammation in lung cancer outcomes, for both local and advanced disease [10,14].
Our study included 268 patients who underwent resection and prospective follow-up for at least 5 years, demonstrates that a lymphocyte-to-monocyte ratio ≥ 2.5 is an independent positive prognostic factor for disease-free survival and overall survival. Although this ratio has been less studied in cancer in general and in bronchogenic cancer in particular, our findings are in line with those obtained by other groups. Honggang Xi et al [15], in 439 patients with stage I NSCLC, demonstrated a positive association between lymphocyte-to-monocyte ratio and overall survival and a greater risk of distal metastases with lower LMR. However, Asian populations may behave differently from European populations in terms of blood markers, so their results will need to be validated in a Western population.
In 2018, Chen et al [16] published a series of 577 surgical patients in stage IB NSCLC who had undergone pneumonectomy. They found that LMR and PLR were independent prognostic factors for OS. In our series, LMR was an independent prognostic factor for OS and DFS. However, we did not find a statistically significant association for PLR as a prognostic factor. One explanation could be that the patients requiring pneumonectomy are usually patients with larger tumours or with greater intrapulmonary lymph node involvement, so they are likely to have higher baseline levels of inflammation. In our study only 5.2% of the patients had undergone pneumonectomy, while 100% of those in the study by Chen et al had undergone pneumonectomy, with pleural invasion in 39% of the cases.
The immunological basis for our findings is that lymphoid cells play a primordial role in the control, proliferation, and migration of tumour cells [17]. In cervical cancer, it has been observed that lymphocytes act as essential components of the immune response, and low levels of lymphocytes in the peripheral blood and tumour stroma lead to a weaker immune response against the cancer cell [18]. In contrast, the presence of high levels of monocytes and their derivatives induces immunosuppression and tumour neoangiogenesis. In addition, intratumour macrophages, derived directly from tissue monocytes, facilitate tumour cell migration by secreting mediators that degrade the extracellular matrix and attract more intratumour monocytes/macrophages, leading to greater tumour aggressiveness both locally and distally [19-22].
In nonsurgical treatments such as stereotactic radiation therapy, several groups have described the effect of NLR and PLR in terms of local recurrence. Canon et al [10] found that PLR should be used as a prognostic factor for DFS. In our study, we did not find such an association, but we must bear in mind that the inflammatory status in the nonsurgical population is probably different: although in some cases patients decide to decline surgery, in many cases they are unsuitable for surgery due to comorbidities.
The interaction between nutritional status, systemic inflammatory status and tumour inflammatory status plays a key role in postoperative outcomes and prognosis in patients with lung cancer [23]. This explains why a higher or lower lymphocyte-to-monocyte ratio confers better or worse prognosis of the disease among patients undergoing surgery, who theoretically will have better long-term outcomes.
The present study has the limitations of being a single-centre retrospective study; also, although the preoperative testing that was used to obtain the ratios was the same for all patients, the findings have not been validated in an independent cohort. The appropriate cut-off point for the ratio is difficult to establish, but according to our results, the value with the greatest sensitivity and specificity was 2.5; values above or below this showed significant differences in overall survival and disease-free survival, in line with other published studies [15-17,24, 25].
The number of patients included, more than 200, the consistency of the blood testing method, the follow-up time and the prospective format of data recording make the data presented relevant for future research.