The Safety and Efficacy of Immunotherapy With Anti-programmed Cell Death 1 Monoclonal Antibody for Lung Cancer Complicated With Mycobacterium Tuberculosis Infection

Jinpeng Shi; Jiayu Li; Qi Wang; Xiaomin Cheng; He Du; Ruoshuang Han; Xuefei Li; Chao Zhao; Guanghui Gao; Yayi He; Xiaoxia Chen; Chunxia Su; Shengxiang Ren; Fengying Wu; Zhemin Zhang; Caicun Zhou


Transl Lung Cancer Res. 2021;10(10):3929-3942. 

In This Article

Abstract and Introduction


Background: Anti-programmed cell death 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) immunotherapy has boosted the prognosis in advanced lung cancer. Meanwhile, accumulating cases showed the correlation between tuberculosis (TB) reactivation and anti-PD-1/PD-L1 immunotherapy. However, the safety and efficacy of anti-PD-1/PD-L1 immunotherapy for lung cancer complicated with TB infection could only be learned from real-world data.

Methods: We retrospectively analyzed 562 patients with advanced lung cancer who received anti-PD-1/PD-L1 immunotherapy at Shanghai Pulmonary Hospital from 2015 to 2019, including 13 patients with TB infection. Besides, relevant literature reviews were performed online to analyze the safety and efficacy of immunotherapy and to explore the appropriate treatment strategies in this specific population.

Results: In our cohort, the initiation of anti-PD-1/PD-L1 immunotherapy was from June 2015 to December 2019. Among them, 13 patients had TB infection prior to immunotherapy including 11 latent TB and 2 active TB, and all of them were treated with anti-PD-1 immunotherapy. Patients with active TB infection were treated with concurrent anti-TB and anti-PD-1 treatments, and the remaining received either mono-immunotherapy or combined immunotherapy. Neither reactivation of latent TB nor progression of active TB was monitored in our cohort during immunotherapy. Severe immune-related adverse events (irAEs) were diagnosed in two patients. Treatment strategies such as discontinuation of immunotherapy and administration of corticosteroids were provided timely, and one with latent TB infection got gradually improved, but the other one with active TB died quickly. The median progression-free survival (PFS) was 5.5 months for tumor immunotherapy in our cohort. However, the PFS of immunotherapy was merely 2.1 and 2.2 months in lung cancer patients with active TB infection.

Conclusions: Immunotherapy is relatively safe for lung cancer patients complicated with previously treated latent TB, and the efficacy of immunotherapy in this specified population is not inferior to that in lung cancer patients without TB infection. TB screening before anti-PD-1/PD-L1 immunotherapy is strongly recommended, and irAEs should be monitored more cautiously in lung cancer patients with active TB infection.


Immune checkpoint inhibitors (ICIs) targeting programmed cell death 1 (PD-1) and its ligand (PD-L1) have shifted the paradigm in various solid malignancies, especially in non-small cell lung cancer (NSCLC).[1–6] It is well known that the binding of co-inhibitory receptor PD-1 with its ligand PD-L1 will attenuate the priming, the proliferation and the cytotoxic capacity of T cells.[7,8] Therefore, tumor cells evade host immune surveillance and escape tumor neutralization through the PD-1/PD-L1 axis.[9] In recent years, immunotherapy with anti-PD-1/PD-L1 monoclonal antibodies (mAbs) has made a breakthrough in NSCLC, and the 5-year survival rate of advanced NSCLC has significantly increased from less than 5% to 23.2%.[10,11]

Immune checkpoint molecules on T cells, such as PD-1 and cytotoxic T lymphocyte antigen 4 (CTLA-4) will also be up-regulated during chronic infectious diseases. The success of immunotherapy in cancer, especially anti-PD-1/PD-L1 mAbs which can restore and enhance the function of T cells, has aroused people's interest in trying immunotherapy to treat chronic infectious diseases.[12] However, growing evidences show anti-PD-1/PD-L1 immunotherapy leads to tuberculosis (TB) reactivation,[13–28] which arouse the awareness of physicians about the safety of immunotherapy and immune-related adverse events (irAEs).

According to the 2020 World Health Organization (WHO) global TB report (, in 2019, an estimated 10.0 million people fell ill with TB, 1.2 million TB deaths among human immunodeficiency virus (HIV)-negative people, and an additional 208,000 deaths among HIV-positive people. China is the second highest TB burden country, accounting for 8.4% cases in total globally. Accumulating data support the view that TB is a risk factor for the development of lung cancer,[29–32] and in China where both TB and lung cancer are prevalent, the co-existence of TB with lung cancer is not rare, which brings great challenges to the treatment of patients, especially in the era of tumor immunotherapy. In clinical practice, the following issues are worth noting. Will the excessive activation of T cells and the release of cytokines induced by anti-PD-1/PD-L1 mAbs activate the latent TB lesions leading to TB recurrence, or deterioration the current TB situation? Will anti-TB therapy increase the incidence of irAEs? There have been many clinical trials on immunotherapy for lung cancer, nonetheless, patients with TB are usually excluded from existing trials resulting in a lack of experience in the above-mentioned issues.

Thus, we retrospectively analyzed 562 patients with advanced lung cancer who received anti-PD-1/PD-L1 immunotherapy in our hospital from 2015 to 2019, including 13 patients with TB infection prior to immunotherapy (either latent or active TB infection), and analyzed the safety and efficacy of immunotherapy among these patients.

We present the following article in accordance with the STROBE reporting checklist (available at