Improving lung cancer survival; time to move on

Abstract Background During the past decades, numerous efforts have been made to decrease the death rate among lung cancer patients. Nonetheless, the improvement in long-term survival has been limited and lung cancer is still a devastating disease. Discussion With this article we would like to point out that survival of lung cancer could be strongly improved by controlling two pivotal prognostic factors: stage and treatment. This is corresponding with recent reports that show a decrease in lung cancer mortality by screening programs. In addition, modulation of the patient’s immune system by immunotherapy either as monotherapy or combined with conventional cancer treatments offers the prospect of tailoring treatments much more precisely and has also been shown to lead to a better response to treatment and overall survival of non-small cell lung cancer patients. Summary Since only small improvements in survival can be expected in advanced disease with the use of conventional therapies, more research should be focused on lung cancer screening programs and patient tailored immunotherapy with or without conventional therapies. If these approaches are clinically combined in a standard multidisciplinary policy we might be able to advance the survival of patients with lung cancer.</p

Patient-tailored modulation of the immune system may revolutionize future lung cancer treatment

Abstract Cancer research has devoted most of its energy over the past decades on unraveling the control mechanisms within tumor cells that govern its behavior. From this we know that the onset of cancer is the result of cumulative genetic mutations and epigenetic alterations in tumor cells leading to an unregulated cell cycle, unlimited replicative potential and the possibility for tissue invasion and metastasis. Until recently it was often thought that tumors are more or less undetected or tolerated by the patient’s immune system causing the neoplastic cells to divide and spread without resistance. However, it is without any doubt that the tumor environment contains a wide variety of recruited host immune cells. These tumor infiltrating immune cells influence anti-tumor responses in opposing ways and emerges as a critical regulator of tumor growth. Here we provide a summary of the relevant immunological cell types and their complex and dynamic roles within an established tumor microenvironment. For this, we focus on both the systemic compartment as well as the local presence within the tumor microenvironment of late-stage non-small cell lung cancer (NSCLC), admitting that this multifaceted cellular composition will be different from earlier stages of the disease, between NSCLC patients. Understanding the paradoxical role that the immune system plays in cancer and increasing options for their modulation may alter the odds in favor of a more effective anti-tumor immune response. We predict that the future standard of care of lung cancer will involve patient-tailor-made combination therapies that associate (traditional) chemotherapeutic drugs and biologicals with immune modulating agents and in this way complement the therapeutic armamentarium for this disease.</p

Tumor derived factors influence macrophages towards a M2 phenotype to varying degrees.

<p>Relative mRNA expression levels of IL-10 (a), CD163 (b), CD80 (c), HLA-DR (d), PD-L1 (e), and Arginase-1/iNOS (NOS2) ratio (f) in macrophages cultured in six mesothelioma cell line conditioned media (T1 - T6) compared to standard M1 and M2 conditions.</p

Correlation between CD68 (a) count or CD 163 (b) count and OS in both surgery and non-surgery groups.

<p>The CD68 count does not correlate with OS (Pearson r -0.07, p = 0.81), the CD163 count shows an inverse trend with OS (Pearson r -0.33, p = 0.22).</p

Patient characteristics.

<p>Patient characteristics.</p

Correlation between CD163/CD68 ratio in tumor in both surgery and non-surgery patients and OS.

<p>This ratio is significantly negatively correlated with OS in the total patient group (Pearson r -0.72, p<0.05).</p

Representative image of CD8 staining in the tumor biopsy of one MPM patient.

<p>Representative image of CD8 staining in the tumor biopsy of one MPM patient.</p