In June 2026, a team led by Xiang Yang, Director of the Gynecological Oncology Center at Peking Union Medical College Hospital (PUMCH), published a Review Article on the tumor immune microenvironment (TIME) of cervical cancer in BBA – Reviews on Cancer. The review points out that cervical cancer cannot be treated with a one-size-fits-all approach: its distinct histological subtypes — squamous cell carcinoma (SCC), adenocarcinoma (ADC), neuroendocrine carcinoma, and others — differ fundamentally in their immune microenvironments. These differences shape not only tumor invasiveness and patient prognosis, but also directly influence the efficacy of immunotherapies, including PD-1 inhibitors. Xiang Yang's team argues that cervical cancer immunotherapy must shift from a "pathology-driven" approach toward one guided by immune microenvironment phenotype, ushering in a new era of precision treatment. 

The team summarized the immune characteristics of the major histological subtypes of cervical cancer, focusing on immune cell composition, stromal architecture, and metabolic influences. The two most common histological types, squamous cell carcinoma (SCC) and adenocarcinoma (ADC), show starkly different immune microenvironments. HPV-associated SCC typically presents an "immune-inflamed" or "immune-active" microenvironment, whereas HPV-associated ADC tends to display an "immune-excluded" or "immune-desert" phenotype.

Certain rare cervical cancer subtypes associated with poorer prognosis — including HPV-independent gastric-type adenocarcinoma (GAS), clear cell carcinoma (CCCC), and neuroendocrine carcinoma of the cervix (NECC) — present an even more challenging immune microenvironment. HPV-independent ADCs, gastric-type ADC in particular, typically show a classic immune-excluded microenvironment. In neuroendocrine carcinoma of the cervix, immune cells are nearly absent from the tumor, leaving it almost entirely unresponsive to current mainstream immunotherapies.

The review examines in depth how the cytokine landscape plays a central role in shaping the immune microenvironment across cervical cancer subtypes. In SCC, the Th1/cytotoxic axis predominates: high expression of interferon-gamma (IFN-γ) and interleukin-12 (IL-12) effectively activates the antitumor activity of CD8+ T cells, while chemokines such as CXCL9 and CXCL10 recruit large numbers of effector T cells into the tumor core. In ADC, particularly the HPV-independent subtypes, the immune microenvironment is instead dominated by immunosuppressive cytokines such as transforming growth factor-beta (TGF-β) and interleukin-10 (IL-10). These cytokines not only directly suppress T-cell function but also promote epithelial-mesenchymal transition (EMT) and angiogenesis, creating conditions favorable to tumor invasion and metastasis.

Building on these findings, the article proposes clinically relevant treatment strategies. For SCC, whose immune microenvironment is already "active", the current standard of care — PD-1 inhibitors combined with chemotherapy — is highly effective, and dual immunotherapy combinations may be worth exploring further to overcome resistance. For adenocarcinoma and neuroendocrine carcinoma with immune-excluded or immune-desert immune microenvironment, PD-1 inhibitors alone are far from sufficient; these subtypes require combination strategies involving anti-angiogenic agents, targeted therapies against specific targets, and cell therapy.

Xiang Yang pointed out that heterogeneity in the TIME plays a decisive role in tumor progression, immune evasion, and overall treatment response. Cervical cancer exhibits temporal plasticity and spatial heterogeneity as the disease progresses and under therapeutic pressure, posing a major challenge for clinical management. Incorporating findings on the TIME into clinical decision-making could shift cervical cancer care toward a subtype-specific precision treatment model — a key breakthrough for improving survival in patients with advanced, recurrent, and rare forms of cervical cancer.

Written by and pictures courtesy of the Gynecological Oncology Center
Edited by Fu Tanping and Chen Xiao
Chief editor Duan Wenli
Supervised by Wu Peixin