Research paperMHC class II expression in lung cancer
Introduction
Lung cancer is the leading cause of cancer death worldwide [1]. Chemotherapy as a standard first line therapy has a poor prognosis. Targeted therapy offers new treatment opportunities for advanced non-small cell lung cancer (NSCLC) [2], [3], [4]. However, only a small population harbors driving mutations such as epidermal growth factor receptor (EGFR) activating mutation could benefit from these targeted therapies. Moreover, acquired resistance to targeted drugs remains big obstacle to prolonging survival [4]. Therefore, other effective therapeutic strategies for patients with advanced NSCLC are urgently needed.
Recently, anti-PD 1 or anti-PD L1 antibodies have shown promising results in cancers including renal, lung and melanoma [5], [6], [7], [8], [9]. Unfortunately, less than one quarter of patients are candidates for anti-PD 1/PD L1 therapy, other strategies, such as regulating other checkpoint factors, should be investigated further.
Major histocompatibility complex (MHC) Class II could internalize, process, and present an antigen to the helper T-cell. The antigens presented by Class II peptides are derived from extracellular proteins. Loading of a MHC Class II molecule occurs by phagocytosis; extracellular proteins are endocytosed, digested in lysosomes, and the resulting epitopic peptide fragments are loaded onto MHC Class II molecules prior to their migration to the cell surface. MHC Class II is constitutively expressed in professional, immune antigen presenting cells, but may also be induced on other cells by interferon γ [10]. This antigen has a restricted tissue distribution and is present primarily on immune cells such as B-lymphocytes, activated T-lymphocytes, monocytes/macrophages, and dendritic cells [11], [12].SCLC cell lines were described as having low or absent expression of MHC Class I major histocompatibility complex antigens [13]. Until now, we didn’t know the expression of MHC Class II in lung cancer. In this study, we described the protein expression of MHC class II in patients with lung cancer and its association with survival.
Section snippets
Cell lines
Two tissue micro arrays (TMAs) containing 55 NSCLC cell lines and 42 SCLC cell lines were produced in the Hirsch Lab. Cell lines were grown in RPMI-1640 media with 10% fetal bovine serum. Cells were harvested, fixed overnight, mixed with 0.9% agarose then allowed to solidify at room temperature for at least 5 min. Each solidified agar pellet was gently placed in a cassette and submerged in 70% ethyl alcohol. The pellets were processed and embedded in paraffin blocks. Cores were taken from each
MHC class II in lung cancer cells and its correlation with E746-A750del, L858R EGFR, ALK fusion and ROS1 rearrangement
Seven (12.7%) NSCLC cell lines were expressed MHC class II (Fig. 1.). None of the SCLC cell lines were found to be MHC Class II, E746-A750del, L858R EGFR, ALK fusion or ROS1-rearrangement positive. There was no correlation between MHC Class II expression and EGFR E746-A750del (P = 0.116), L858R (P = 0.571), ALK fusion (P = 0.341) and ROS1-rearrangement (P = 0.127) in NSCLC cell lines (Table S1.).
MHC class II protein expression in lung cancer tumor tissues
We assessed in one hundred and thirty-nine lung cancer samples from Hirsch Lab for MHC Class II expression.
Discussion
In our study, we assayed the expression of MHC Class II protein on tumor cells and TILs in NSCLC patients and described its association with survival. Additionally, we found MHC Class II was expressed in both NSCLC cell lines and tissues. However, MHC Class II expression was absent in SCLC cell lines and tissue tumor cells. Moreover, SCLC TILs expressed MHC Class II less than NSCLC TILs. Higher MHC Class II expression on TILs was correlated with better prognosis in patients with NSCLC.
MHC Class
Conflicts and interests
The authors declare that they have no competing interests.
Funding
This project was supported by the IASLC Young Investigator Award, the Pia and Fred R. Hirsch Endowed Chair at the University of Colorado, and Shanghai Pujiang Program (17PJD036). Major disease clinical skills enhancement program of three year action plan for promoting clinical skills and clinical innovation in municipal hospitals, Shanghai Shen Kang Hospital Development Center (16CR1001A).
Acknowledgements
The authors would like to thank than Fred R Hirsch and Caicun Zhou for their support.
References (32)
- et al.
Final overall survival results from a randomised, phase III study of erlotinib versus chemotherapy as first-line treatment of EGFR mutation-positive advanced non-small-cell lung cancer (OPTIMAL, CTONG-0802)
Ann. Oncol.
(2015) - et al.
Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial
Lancet Oncol.
(2015) - et al.
Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial
Lancet Oncol.
(2015) - et al.
Interferon-mediated in vivo induction of beta 2-microglobulin on small-cell lung cancers and mid-gut carcinoids
Clin. Immunol. Immunopathol.
(1986) - et al.
On the relevance of a testing algorithm for the detection of ROS1-rearranged lung adenocarcinomas
Lung Cancer.
(2014) - et al.
Correlation of IHC and FISH for ALK gene rearrangement in non-small cell lung carcinoma: IHC score algorithm for FISH
J. Thorac. Oncol.
(2011) - et al.
The B7-H1 (PD-L1) T lymphocyte-inhibitory molecule is expressed in breast cancer patients with infiltrating ductal carcinoma: correlation with important high-risk prognostic factors
Neoplasia
(2006) - et al.
Natural history of HLA expression during tumour development
Immunol. Today
(1993) - et al.
Lung cancer incidence and mortality in China, 2009
Thorac. Cancer
(2013) - et al.
Erlotinib for frontline treatment of advanced non-small cell lung cancer: a phase II study
Clin. Cancer Res.
(2006)