New research spotlights cellular immunity in lung cancer

By Naveed Saleh, MD, MS
Published December 16, 2020

Key Takeaways

Lung cancer is still the leading cause of cancer deaths worldwide, according to the WHO, and non-small cell lung cancer (NSCLC) is the predominant form—accounting for about 85% of all lung cancer cases. For patients with NSCLC, the 5-year survival rate is 24%. A preclinical study published recently in the Annals of Translational Medicine sheds light on cellular immunity in lung cancer patients.

Researchers examined the effects of transforming growth factor 1 (TGF-β1) on cellular immunity in lung adenocarcinoma cell lines and in peripheral blood mononuclear cells (PBMCs). Of note, TGF-β1 is a complex cytokine that regulates the division and differentiation of tumor cells.

The authors wrote that “TGF-β1 was highly expressed in patients with NSCLC, which could promote the growth, invasion, and metastasis of NSCLC. Comparable results have been obtained in vitro and in vivo in studies of colon cancer, liver cancer, gastric cancer, lung cancer, and prostate cancer.” 

Investigators cultured the A549 cell line and PBMCs with varying concentrations of TGF-β1 to observe changes in the morphology of A549 cells. They also analyzed levels of interleukin (IL)-2, IL-4, IL-6, IL-10, IFN-γ, and TNF, as well as the number of CD antigens in PBMCs. 

The researchers found that TGF-β1 induced A549, which led to epithelial-to-mesenchymal transition and enhanced migration and infiltration. Concurrently, TGF-β1 depressed the growth and proliferation of PBMCs, stunted T-cell activation, and hastened the apoptosis of PBMCs. Furthermore, TGF-β1 has the ability to inhibit A549 Th1-related cytokines, enhance Th2-related cytokines, and interfere with Th1/Th2 levels, thus leading to Th1 cellular-dominated immunity decline. 

The authors wrote, “The metastasis ability of tumor cells depends on the loss of cell-to-cell junctions and the acquisition of [fibroblast] characteristics, a process known as epithelial-interstitial transformation.” 

Providing further background information, they noted that the escape of lung cancer cells from immune surveillance is inextricably tied to the occurrence, development, metastasis, recurrence, and prognosis of lung cancer. CD 4 cells act as essential helper T lymphocytes (eg, T help, Th cells), which, depending on cytokines released, are subdivided into Th1 cells and Th2 cells. Experts hypothesize that the level of Th1/Th2 is linked to the escape of lung cancer cells from immune surveillance.

In those with lung cancer, immune response is dominated by cellular immunity, and cells that play a role include T lymphocytes, NK cells, and macrophages. Previous research has demonstrated that in cancer patients with low cellular immune function, T lymphocytes and NK cell activity is lower. Moreover, the malignant tumor produces relatively large quantities of tumor-derived immune-suppressive factor (TDSF), an immunosuppressant that is a principal cause of immune dysfunction with respect to malignant tumors. The immunosuppressant effect of TGF-β1 is 104 to 106 times greater than that of cyclosporine A.

“In this study,” the authors wrote, “the number of cell morphology EMT [epithelial-mesenchymal transitions] decreased and the cell membrane integrity was damaged at the same time, which contradicted other reports that TGF-β1 did not affect the proliferation of A549 cells, which may be related to the addition of PBMCs. In the tumor microenvironment, the apoptosis effect of CD4 + T cells on A549 cells is related.”

Metastatic NSCLC severely impacts patient quality of life secondary to considerable symptom burden. In the past year, the FDA moved forward to approve two new first-line treatments for patients with NSCLC: atezolizumab (Tecentriq) in combination with chemotherapy (paclitaxel protein-bound [Abraxane] and carboplatin) for the initial treatment of adults with metastatic NSCLC; and nivolumab (Opdivo) in combination with ipilimumab (Yervoy) for the treatment of metastatic or recurrent NSCLC.  

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