Histological transformation into SCLC: An important resistance mechanism of NSCLC upon immunotherapy

Jiao Zeng; Xinjing Ding; Jianghua Ding; Xin Wang

doi:10.3389/fimmu.2023.1275957

Histological transformation into SCLC: An important resistance mechanism of NSCLC upon immunotherapy

Front Immunol. 2023 Oct 30:14:1275957. doi: 10.3389/fimmu.2023.1275957. eCollection 2023.

Authors

Jiao Zeng^#^{1

2}, Xinjing Ding^#³, Jianghua Ding¹, Xin Wang⁴

Affiliations

¹ Department of Hematology & Oncology, Jiujiang University Affiliated Hospital, Jiujiang, Jiangxi, China.
² Graduate Department, Gannan Medical University, Ganzhou, Jiangxi, China.
³ Department of Oncology, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
⁴ Department of Social Medicine and Public Health, School of Basic Medicine, Jiujiang University, Jiujiang, Jiangxi, China.

^# Contributed equally.

Abstract

The phenomenon of histological transformation has been widely reported in advanced non-small cell lung cancer (NSCLC) with EGFR mutations following the failure of EGFR-TKI treatment. Recent evidence suggests that similar histological changes can also occur in advanced NSCLC without driver gene mutations after developing resistance to immunotherapy. In this review, it was found that 66.7% of cases with immunotherapy-induced histological transformation were classified as lung squamous cell carcinoma (LSCC), while histological conversion into lung adenocarcinoma (LUAD) without EGFR or ALK gene mutations has rarely been reported. There have been sporadic reports on the occurrence of mutual transformation between LUAD and LSCC. The histological conversion from NSCLC into small cell lung cancer (SCLC) appears to be significantly underestimated, likely due to the infrequency of re-biopsy following the development of immunotherapy resistance. Several studies have reported a close association between the transformation and mutations at TP53 and the RB1 splice site, as well as the loss of an FBXW7 mutation. However, the exact mechanisms underlying this conversion remain unclear. Currently, there is a lack of guidelines for the management of transformed SCLC from NSCLC following immunotherapy, with chemotherapy being the most commonly employed treatment approach.

Keywords: histological transformation; immunotherapy; non-small cell lung cancer; resistance; small cell lung cancer.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Adenocarcinoma of Lung* / genetics
Carcinoma, Non-Small-Cell Lung* / drug therapy
Carcinoma, Non-Small-Cell Lung* / therapy
ErbB Receptors / genetics
Humans
Immunotherapy
Lung Neoplasms* / drug therapy
Lung Neoplasms* / genetics
Small Cell Lung Carcinoma* / drug therapy
Small Cell Lung Carcinoma* / therapy

Substances

ErbB Receptors

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This paper received funding from the Key project of Jiangxi Natural Science Foundation (No. 20224ACB206038), China.